ArticleLiterature Review

Effects of Alcohol on the Endocrine System

September 2013
Endocrinology and Metabolism Clinics of North America 42(3):593-615

DOI:10.1016/j.ecl.2013.05.008

Source
PubMed

Authors:

Nadia Rachdaoui

NutrArgan

Dipak Sarkar

Rutgers, The State University of New Jersey

Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine, and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiologic and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease, and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system.

Effect of environmental factors on occurrence of male infertility

Article

Full-text available

Feb 2021

Introduction Infertility is the inability of a sexually active couple to achieve pregnancy within one year of regular intercourse without the use of contraception. At present, this problem concerns approximately 10–20% of couples. Among the causes of male infertility are distinguished pre-testicular, testicular and extra-testicular factors. Objective The aim of the study was to review the available literature data concerning the effect of individual, selected environmental factors on the phenomenon of infertility in the male population. Brief description of the state of knowledge Many studies confirmed a progressive deterioration of sperm quality in the male population. Among the factors responsible for the occurrence of this phenomenon are heavy metals present in the environment, such as lead, mercury and cadmium, commonly used pesticides, bisphenol A, as well as dioxins and furans, classified as persistent organic pollutants. These substances exert a negative effect on the body's hormonal balance, and also damage Sertoli and Leydig cells, which may result in reduced sperm count and motility. Life style also plays an important role in maintaining male fertility. Unhealthy diet, tobacco smoking and alcohol consumption reduce testosterone levels and damage the genetic material of sperm. Summary Many chemicals can negatively affect male fertility. Efforts should be made to reduce exposure to pollutants in the environment, improve life style, undertake physical activity, and abstain from stimulants

Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells

Article

Full-text available

Dec 2022

Estrogen receptor alpha positive (ERα+) breast cancers are refractory to immune checkpoint blocker (ICB) monotherapy, while ICBs are part of a standard of care for triple negative breast cancers (TNBCs). Besides tumor ERα expression, another difference between the two types of breast cancers is that only ERα+ patients exhibit elevated tumor estradiol (E2) levels, compared with surrounding normal tissue. Recent evidence suggests that inhibition of ERα or activation of ERβ or G protein-coupled estrogen receptor (GPER) in immune cells in the tumor microenvironment (TME) increases tumor CD8+ T cell infiltration and boosts cancer ICB response. Ovarian and adipose-produced estrogens activate all three ERs equally, but plant estrogens (phytochemicals) preferentially activate ERβ or GPER. The gut microbiota is a key player in determining response to ICBs, and high abundance of Firmicutes and high fecal levels of short chain fatty acids (SCFAs) that are mainly produced by Firmicutes, are linked to improved effectiveness of ICB therapy. Interestingly, the gut microbiota of ERα+ breast cancer patients contain significantly lower abundance of Firmicutes species than the gut microbiota of TNBC patients. Many factors modify the gut microbiota, especially diet. The gut microbiota altering diets include (i) foods high in ERβ and GPER activating plant phytochemicals or (ii) SCFAs producing fiber that also reduces circulating estrogen levels, (iii) estrogen levels reducing fasting/caloric restriction, or (iv) ketogenic diet which reduces fecal SCFA levels but increases hepatic production of SCFA receptor activating ketone bodies. It is thus possible that certain foods or dietary patterns can modify both the gut microbiota and activation of the estrogen receptors in the tumor immune cells, and consequently regulate the effectiveness of ICB therapy against cancers.

The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease

Article

Full-text available

Dec 2020
INT J MOL SCI

Ethanol misuse is frequently associated with a multitude of profound medical conditions, contributing to health-, individual-and social-related damage. A particularly dangerous threat from this classification is coined as alcoholic liver disease (ALD), a liver condition caused by prolonged alcohol overconsumption, involving several pathological stages induced by alcohol metabolic byproducts and sustained cellular intoxication. Molecular, pathological mechanisms of ALD principally root in the innate immunity system and are especially associated with enhanced functionality of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. NF-κB is an interesting and convoluted DNA transcription regulator, promoting both anti-inflammatory and pro-inflammatory gene expression. Thus, the abundancy of studies in recent years underlines the importance of NF-κB in inflammatory responses and the mechanistic stimulation of inner molecular motifs within the factor components. Hereby, in the following review, we would like to put emphasis on the correlation between the NF-κB inflammation signaling pathway and ALD progression. We will provide the reader with the current knowledge regarding the chronic and acute alcohol consumption patterns, the molecular mechanisms of ALD development, the involvement of the NF-κB pathway and its enzymatic regulators. Therefore, we review various experimental in vitro and in vivo studies regarding the research on ALD, including the recent active compound treatments and the genetic modification approach. Furthermore, our investigation covers a few human studies.

Alcohol as an early life stressor: Epigenetics, metabolic, neuroendocrine and neurobehavioral implications

Article

Aug 2020

Ethanol exposure during gestation is an early life stressor that profoundly dysregulates structure and function s of the embryonal nervous system, altering the cognitive and behavioral development. Such dysregulation is also achieved by epigenetic mechanisms, which, altering the chromatin structure , redraw the entire pattern of gene expression . In parallel, an oxidative stress response at the cellular level and a global upregulation of neuroendocrine stress response, regulated by the HPA axis, exist and persist in adulthood. This neurobehavioral framework matches those observed in other psychiatric diseases such as mood diseases, depression, autism; those early life stressing events, although probably triggered by specific and different epigenetic mechanisms, give rise to largely overlapping neurobehavioral phenotypes. An early diagnosis of prenatal alcohol exposure, using reliable markers of ethanol intake, together with a deeper understanding of the pathogenic mechanisms, some of them reversible by their nature, can offer a temporal “window” of intervention. Supplementing mother’s diet with protective and antioxidant substances in addition to supportive psychological therapies can protect newborns from being affected.

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

Article

Full-text available

Apr 2020
PLOS ONE

Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept.

Smoke, alcohol and drug addiction and female fertility

Article

Full-text available

Mar 2020
REPROD BIOL ENDOCRIN

Background: Considerable interest has been gathered on the relevant impact of preventable factors, including incorrect lifestyle and unhealthy habits, on female fertility. Smoking, alcohol and addictive drugs consumption represent a major concern, given the broad range of diseases which might be favored or exacerbated by these dependable attitudes. Despite the well-characterized effects of prenatal exposure on pregnancy outcomes and fetus health, a substantial proportion of women of reproductive age is still concerned with these habits. At present, the impact of smoke, alcohol and addictive drugs on women fertility, and, particularly, the specific targets and underlying mechanisms, are still poorly understood or debated, mainly due to the scarcity of well-designed studies, and to numerous biases. Objective: The current review will provide a comprehensive overview of clinical and experimental studies in humans and animals addressing the impact of smoke, alcohol and addictive drugs on female fertility, by also embracing effects on ovary, oviduct, and uterus, with particular reference to primary endpoints such as ovarian reserve, steroidogenesis, ovulation and menstrual cycle, oviduct function and uterus receptivity and implantation. A brief focus on polycystic ovary syndrome and endometriosis will be also included. Methods: A Pubmed literature search was performed with selected keywords; articles were individually retrieved by each author. No limitation was set for publication date. Articles in languages other than English were excluded. Additional articles were retrieved from references list of selected manuscripts. Results and conclusions: Currently, the most consistent evidences of a detrimental effect of smoke, alcohol and addictive drugs on specific domains of the female reproductive function are provided by experimental studies in animals. Overall, clinical studies suggest that smoking is associated to decreased fertility, although causal inference should be further demonstrated. Studies addressing the effect of alcohol consumption on female fertility provide conflicting results, although the majority reported lack of a correlation. Extremely scarce studies investigated the effects of addictive drugs on female fertility, and the specific actions of selected drugs have been difficult to address, due to multidrug consumption.

A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target

Article

Full-text available

Aug 2023

Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen’s contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism–gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application.

Developmental Changes of Duckling Liver and Isolation of Primary Hepatocytes

Article

Full-text available

May 2023

The liver is the main site of fat synthesis and plays an important role in the study of fat deposition in poultry. In this study, we investigated the developmental changes of duckling livers and isolated primary duck hepatocytes. Firstly, we observed morphological changes in duckling livers from the embryonic period to the first week after hatching. Liver weight increased with age. Hematoxylin-eosin and Oil Red O staining analyses showed that hepatic lipids increased gradually during the embryonic period and declined post-hatching. Liver samples were collected from 21-day-old duck embryos for hepatocyte isolation. The hepatocytes showed limited self-renewal and proliferative ability and were maintained in culture for up to 7 days. Typical parenchymal morphology, with a characteristic polygonal shape, appeared after two days of culture. Periodic acid-Schiff (PAS) staining analysis confirmed the characteristics of duck embryo hepatocytes. PCR analysis showed that these cells from duck embryos expressed the liver cell markers ALB and CD36. Immunohistochemical staining and immunofluorescence analysis also confirmed ALB and CK18 expression. Our findings provide a novel insight regarding in vitro cell culture and the characteristics of hepatocytes from avian species, which could enable further studies concerning specific research on duck lipid metabolism.

Relationship between Substance use and Endocrine Disorders: A Narrative Review

Article

Full-text available

Apr 2023

Substance use disorder is one of the significant public health concerns and the co-morbidity with endocrine disorders has the potential to cause adverse outcomes. There is a definite link between substance use and dysregulation of the endocrine system at a level of causation, association, management, and drug interaction. It has been seen that the screening of substance use while managing endocrine disorders is a must. Also, integrated management of both of these chronic conditions with collaborative care approach can not only help in effective management but also improve the outcomes in terms of mortality, cost-effectiveness, stigma, and financial burden. Though considered important this common area seems to be understudied. Hence we recommend that this co-occurrence of substance use and endocrine disorders should be studied and guidelines be developed for effective management.

Thyroid Function in Liver Cirrhosis: Is It affected? A Case Control Study

Article

Full-text available

Jan 2023

Evaluation of Thyroid Functions in Cirrhotic Patients with Refractory Ascites

Article

Sep 2022

Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms

Article

Full-text available

Sep 2022

Hong Lu

Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients.

study on thyroid functions in chronic liver disease: A one year prospective study

Article

Full-text available

Jul 2022

In the present study, thyroid functions have been evaluated with all the clinically available indices and confirms the abnormalities in many parameters of thyroid function test in chronic liver disease patients. However euthyroid state is maintained virtually in all patients, probably as a result of low normal Free T3 and high normal FT4. Furthermore, serum T3 concentration appear to directly correlate with the severity of liver dysfunction.

Lutein Can Alleviate Oxidative Stress, Inflammation, and Apoptosis Induced by Excessive Alcohol to Ameliorate Reproductive Damage in Male Rats

Article

Full-text available

Jun 2022

Chronic excessive alcohol intake may lead to male reproductive damage. Lutein is a carotenoid compound with antioxidant activity. The purpose of this study was to observe the effect of lutein supplementation on male reproductive damage caused by excessive alcohol intake. In this study, an animal model of excessive drinking (12 mL/(kg.bw.d)) for 12 weeks was established and supplemented with different doses of lutein (12, 24, 48 mg/(kg.bw.d)). The results showed that the body weight, sperm quality, sex hormones (FSH, testosterone), and antioxidant markers (GSH-Px) decreased significantly, while MDA and inflammatory factors (IL-6, TNF-α) increased significantly in the alcohol model group when compared to the normal control group. After 12 weeks of high-dose lutein supplementation with 48mg/(kg.bw.d), the spermatogenic ability, testosterone level, and the activity of marker enzymes reflecting testicular injury were improved. In addition, high-dose lutein supplementation downregulated the NF-κB and the pro-apoptosis biomarkers (Bax, Cytc and caspase-3), whereas it upregulated the expression of Nrf2/HO-1 and the anti-apoptotic molecule Bcl-2. These findings were fully supported by analyzing the testicular histopathology and by measuring germ cell apoptosis. In conclusion, lutein protects against reproductive injury induced by excessive alcohol through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

The maternal-placental-fetal interface: Adaptations of the HPA axis and immune mediators following maternal stress and prenatal alcohol exposure

Article

May 2022
EXP NEUROL

This review addresses underlying physiological, cellular, and molecular factors that alter the developing fetal brain stress circuits and responses of the hypothalamic-pituitary-adrenal (HPA) axis caused by maternal stress and prenatal alcohol exposure (PAE). An emphasis is placed on the contribution of the placenta following maternal stress separately, and as a co-occurrence with PAE. Altered fetal HPA axis ultimately results in dysregulation of the brain stress-response system long after birth and possibly lifelong. Additional consideration of the role of placentally-derived endocrine and sex hormones, as well as a brief discussion of epigenetic mechanisms of altered placental expression of genes encoding the glucocorticoid receptor and the enzymes 11β-HSD that rapidly convert glucocorticoids into its active or inactive forms are reviewed. Data highlighting the strong, reciprocal interactions between the neuroimmune and neuroendocrine systems during fetal development that are impacted by maternal stress and PAE are considered, emphasizing the role of the placenta as a key contributor to the dysregulation of these systems. In view of the maternal-placental-fetal interface, important physiological, cellular, and molecular factors underlying later life dysregulated stress responses are additionally considered. Literature from animal models of PAE and maternal stress is reviewed that support clinical observations of the effect of maternal stress and alcohol exposure during fetal development on later-life adult stress responses and associated mood dysregulation. An appreciation of dysregulated stress responses in individuals with fetal alcohol spectrum disorders (FASD) are addressed given the greater prevalence of adult dysregulated stress responses and a greater co-occurrence of mood disorders in individuals diagnosed with FASD.

Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence

Article

Full-text available

Jan 2022

Nahlah Almansour

Triple-negative breast cancer (TNBC) is a kind of breast cancer that lacks estrogen, progesterone, and human epidermal growth factor receptor 2. This cancer is responsible for more than 15–20% of all breast cancers and is of particular research interest as it is therapeutically challenging mainly because of its low response to therapeutics and highly invasive nature. The non-availability of specific treatment options for TNBC is usually managed by conventional therapy, which often leads to relapse. The focus of this review is to provide up-to-date information related to TNBC epidemiology, risk factors, metastasis, different signaling pathways, and the pathways that can be blocked, immune suppressive cells of the TNBC microenvironment, current and investigation therapies, prognosis, and the role of artificial intelligence in TNBC diagnosis. The data presented in this paper may be helpful for researchers working in the field to obtain general and particular information to advance the understanding of TNBC and provide suitable disease management in the future.

Ginger (Zingiber officinale Roscoe) Improves Ethanol- Induced Reproductive Dysfunction by Enhancing Steroidogenesis and Inhibiting Oxidative Stress and Inflammation

Article

Jan 2022
BRAZ ARCH BIOL TECHN

Ginger is traditionally used as a sexual enhancer in folk medicine. Despite extensive studies on the effect of ginger on reproduction, the molecular mechanism of ginger prevention effect on ethanol-induced reproductive disorder is not fully understood. Twenty-four adult male rats were allocated into control, ethanol (4 g/kg of body weight (BW)/day), ginger (250 mg/kg of BW/day) and ginger-ethanol group. Ginger and ethanol were administrated by gavage for 28 days. Testicular concentration of testosterone, TNF-α, and antioxidant enzymes activity and serum concentration of gonadotropins hormone and testosterone were measured. The gene expression of Nrf2 and NF-κB which regulate oxidative damage and inflammation, respectively, and StAR, P450scc and 17βHSD which are involved in testosterone synthesis were detected. Ethanol significantly decreased gonadotropin hormones, oxidative markers, expression of genes involved in testosterone synthesis and Nrf2, and in reverse significantly increased TNF-α, MDA and gene expression of NF-κB compared to control (p<0.05). While ginger could significantly improve all of the above factors HIGHLIGHTS  Ethanol induces reproductive dysfunction.  Ginger (Zingiber officinale Roscoe) improves steroidogenesis.  Ginger inhibits oxidative stress and inflammation.  Ginger improves ethanol-induced reproductive dysfunction. 2 Li, N.; et al. Brazilian Archives of Biology and Technology. Vol.64: e21210035, 2021www.scielo.br/babt compared to the ethanol group (p<0.05). These results were also supported by histological findings. It can be concluded that ginger prevents the ethanol-induced reproductive dysfunction by improving the gonadotropins, oxidative damage and inflammation and the genes involved in testosterone synthesis.

Ginger (Zingiber officinale Roscoe) Improves Ethanol-Induced Reproductive Dysfunction by Enhancing Steroidogenesis and Inhibiting Oxidative Stress and Inflammation

Article

Full-text available

Jan 2021
BRAZ ARCH BIOL TECHN

Abstract Ginger is traditionally used as a sexual enhancer in folk medicine. Despite extensive studies on the effect of ginger on reproduction, the molecular mechanism of ginger prevention effect on ethanol-induced reproductive disorder is not fully understood. Twenty-four adult male ratswereallocated into control, ethanol (4 g/kg of body weight (BW)/day), ginger (250 mg/kg of BW/day) and ginger-ethanol group. Ginger and ethanol were administrated by gavage for 28 days. Testicular concentration of testosterone, TNF-α, and antioxidant enzymes activity and serum concentration of gonadotropins hormone and testosterone were measured. The gene expression of Nrf2 and NF-κB which regulate oxidative damage and inflammation, respectively, and StAR, P450scc and 17βHSD which are involved in testosterone synthesis were detected. Ethanol significantly decreased gonadotropin hormones, oxidative markers, expression of genes involved in testosterone synthesis and Nrf2, and in reverse significantly increased TNF-α, MDA and gene expression of NF-κB compared to control (p

Disrupted circadian expression of beta‐arrestin 2 affects reward‐related µ‐opioid receptor function in alcohol dependence

Article

Dec 2021

There is increasing evidence for a daily rhythm of µ‐opioid receptor (MOR) efficacy and the development of alcohol dependence. Previous studies show that β‐arrestin 2 (bArr2) has an impact on alcohol intake, at least partially mediated via modulation of MOR signaling, which in turn mediates the alcohol rewarding effects. Considering the interplay of circadian rhythms on MOR and alcohol dependence, we aimed to investigate bArr2 in alcohol dependence at different time points of the day/light cycle on the level of bArr2 mRNA (in situ hybridization), MOR availability (receptor autoradiography), and MOR signaling (Damgo‐stimulated G‐protein coupling) in the nucleus accumbens of alcohol‐dependent and non‐dependent Wistar rats. Using a microarray data set we found that bArr2, but not bArr1, shows a diurnal transcription pattern in the accumbens of naïve rats with higher expression levels during the active cycle. In 3‐week abstinent rats, bArr2 is up‐regulated in the accumbens at the beginning of the active cycle (ZT15), whereas no differences were found at the beginning of the inactive cycle (ZT3) compared with controls. This effect was accompanied by a specific down‐regulation of MOR binding in the active cycle. Additionally, we detect a higher receptor coupling during the inactive cycle compared with the active cycle in alcohol‐dependent animals. Together, we report daily rhythmicity for bArr2 expression linked to an inverse pattern of MOR, suggesting an involvement for bArr2 on circadian regulation of G‐protein coupled receptors in alcohol dependence. The presented data may have implications for the development of novel bArr2‐related treatment targets for alcoholism. image

Hospital admissions due to endocrine diseases in Korean male firefighters

Article

Full-text available

Oct 2021

Background: The aim of this study was to investigate the relationship between occupational exposure to various hazards and hospital admission due to endocrine diseases in Korean male firefighters. Methods: From 2000 to 2008, former and current male firefighters registered in the Korean National Emergency Management Agency were investigated based on their hospitalized health insurance admission data for the same period. Admission data for endocrine, nutritional, and metabolic diseases were obtained from the Korean National Health Insurance Service database. Standardized admission ratio (SAR) with reference to the general population of Korean men was analyzed. Results: SAR for firefighters with endocrine, nutritional, and metabolic diseases was 0.56 (95% confidence interval [CI]: 0.49-0.65), which was significantly less than that of the general population of Korean men. For those with endocrine, nutritional, and metabolic diseases, SARs for those with a history of fire suppression tasks and those without experience of fire suppression tasks were 0.58 (95% CI: 0.49-0.68) and 0.53 (95% CI: 0.40-0.70), respectively. Conclusions: The admission rate of Korean male firefighters due to endocrine, nutritional and metabolic diseases was significantly lower than that of the general Korean men population, the hazardous potential of endocrine disruptors remains an open question. Further studies of firefighters with longer follow-up are needed.

Alcohol-Induced Mitochondrial and NADPH Oxidase Mediated ROS Generation Alter Neuroendocrine Status: Role of Pterocarpus Santalinus

Preprint

Full-text available

Sep 2021

The association between oxidative stress and endocrine status with respect to the role of Pterocarpus santalinus (PSE) against alcohol-induced neurotoxicity in rats was investigated. Male albino rats were divided into, control, alcohol treated, alcohol + PSE treated, and PSE treated group. Twenty percent of ethanol (5g/kg body weight/day) was given with and without PSE (250 mg/kg body weight/day) for 60 days. Decreased plasma testosterone, estradiol, thyroid hormones (T 3 and T 4 ), and increased cortisol concentrations in alcohol treated rats were observed. Besides, elevated lipid peroxidation, protein carbonyls, NADPH oxidase (NOX), and cytochrome P-450 (CYP-450) activities, with mitochondrial dysfunction were noticed. Moreover, increased protein expression of the phosphorylated protein kinase C (p-PKC), phospholipase C (p-PLC), and NOX2 with decreased antioxidant status was also noticed in alcohol ingested rats. Administration of PSE to alcohol treated rats reduced oxidative stress by increasing antioxidant status, also modulated mitochondrial dysfunction and protein expression of p-PKC, p-PLC and NOX2. In conclusion, ROS generated via mitochondrial dysfunction causes activation of NOX activity through PLC and PKC dependent pathways leading to more ROS generation, which in turn alters the circulating hormonal levels. The phytocompounds present in PSE confer therapeutic efficacy by scavenging ROS and thereby offer protection.

Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review

Article

Full-text available

Aug 2021

Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50. Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like). The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences.

Mapsci-JEMR-1(2)-008| Research Article Citation: Samarthana V, Mamatha BP. Study of Thyroid Function Tests Incirrhosis of Liver And Correlation of Thyroid Function Tests Levels With Severity of Liver Dysfunction

Article

Full-text available

Jan 2020

Samarthana Vijaykumar

Principles of laboratory investigation for pituitary hormones

Chapter

Jan 2021

Measurement of circulating concentrations of hormones that are secreted directly by the pituitary, or by other glands under the control of pituitary hormones, remains the cornerstone in diagnosis and monitoring of pituitary diseases. However, concentrations without clinical information remain of limited value and can be misleading. The diagnostic importance of these “numbers” increases with each additional piece of information when they are put in a clinical context (e.g., sex, age, clinical findings, medication, but also timing and conditions of sampling, etc.). In addition, transport conditions and technical factors during the analytical process can influence quantitative and qualitative aspects of laboratory results and need to be taken into account for interpretation. The process from drawing a blood sample to interpreting the laboratories report can be divided into three main phases—the preanalytical, the analytical, and the postanalytical phase. Each phase is associated with particular pitfalls which are described in the following.

Study of Thyroid Function Tests in Cirrhosis of Liver And Correlation of Thyroid Function Tests Levels With Severity of Liver Dysfunction

Article

Full-text available

Oct 2020

Mamatha B Patil

Background: One of the leading causes of morbidity and mortality in the world is chronic liver diseases. Thyroid hormones regulate the basal metabolic rate of all cells, including hepatocytes, and thereby modulate hepatic function. The liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effects. Thyroid dysfunction may perturb liver function, liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs. Keeping in mind the above view we have done this study by highlighting the association between thyroid function tests with severity of liver dysfunction in cirrhosis of liver by using child Pugh scoring Methods: All patients aged 30-80 years with cirrhosis of liver who are attending Rajarajeshwari Medical College and Hospital. Detailed history, physical examination and drug history was taken as per pre-designed performa. Relevant investigations were done for assessing thyroid function and liver cirrhosis. Severity of liver dysfunction was graded by using Child Pugh Scoring Results: The prevalence of hypothyroidism among patients with liver cirrhosis was 64%. Majority of the cases had a high TSH and TSH levels were directly correlated severity of liver disease. Total T3 levels were low in majority of the cases and it was inversely correlated with severity of liver disease. FT3 was low in most of the cases with child B and child C score; it was inversely correlated with severity of liver disease. FT3 was found to be a more sensitive marker than total T3 for assessing severity of liver disease. Conclusion: Thyroid dysfunction is common in cirrhosis of liver hence thyroid function tests should be carried out in all cirrhotic patients to assess the severity and prognostication of such patients.

A novel metabolic disorder in the degradation pathway of endogenous methanol due to a mutation in the gene of alcohol dehydrogenase

Article

Full-text available

Feb 2021
CLIN BIOCHEM

Background A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. Results This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1-4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and appeared healthy. Organ evaluations and his laboratory tests were normal. Toxicological evaluation of his blood showed a high methanol level [12.2 mg/dL (3.8 mmol/L), normal range up to 3.5 mg/dL (1.09 mmol/L) while the formaldehyde level was undetectable. The finding of liver function tests that were within normal limits, coupled with a normal eye examination and size of the liver, elevated blood methanol levels and an undetectable formaldehyde level, suggested ADH insufficiency. Adding zinc to the drug regimen 15 mg/daily dramatically reduced the patient’s methanol level and alleviated the abnormal symptoms. When zinc supplementation was discontinued, the patient relapsed into a coma and hemodialysis was once again required. A homozygous mutation in ADH1C gene located at exon 3 was found, and both parents were heterozygous for this mutation. Conclusion Accumulation of methanol due to mutation in ADH1C gene may result in drunkenness and ataxia, and leads to coma. This condition can be successfully treated with zinc supplementation as the cofactor of ADH.

Alcohol-Induced Neuropathy in Chronic Alcoholism: Causes, Pathophysiology, Diagnosis, and Treatment Options

Article

Full-text available

Dec 2020

Purpose of the Review Alcohol abuse causes a wide range of disorders that affect the nervous system. These include confusion, cerebellar ataxia, peripheral neuropathy, and cognitive impairment. Chronic and excessive alcohol consumption is the primary cause of peripheral neuropathy. It is worth noting that peripheral neuropathy has no reliable treatment due to the poor understanding of its pathology. Recent Findings Coasting is a major feature of alcoholic neuropathy, largely due to chronic alcohol abuse. Its major features are hyperalgesia, allodynia, and burning pain. Even though much research was done in this area, still we do not have a full understanding of the mechanism of alcoholic neuropathy. However, some theories have been proposed. These include direct or indirect effects of alcohol metabolites, impaired axonal transport, suppressed excitatory nerve pathway activity, or imbalance in neurotransmitters. Activation of spinal cord microglia, mGlu5 spinal cord receptors, and hypothalamic-pituitary-adrenal axis also seem to be implicated in the pathophysiology of this alcoholic neuropathy. The goal of treatment is to impede further damage to the peripheral nerves while also restoring their normal physiology. Alcohol abstinence, intake of balanced diets, and treatment with medications are suggested including benfotiamine, alpha-lipoic acid, acetyl-L-carnitine, vitamin E, methylcobalamin, myo-inositol, N-acetylcysteine, capsaicin, tricyclic antidepressants, or antiepileptic drugs. Summary This review focuses on the many pathways that play a role in the onset and development of alcohol-induced neuropathy, as well as present the possible treatment strategies of this disorder, providing insights into a further search of new treatment modalities.

Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala

Article

Full-text available

Aug 2020

In human beings, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. Researchers have hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the current study, we examined the long‐term effects of suppressing adolescent gonadal hormone levels in a group of female Lister‐hooded rats via administration of a gonadotropin‐releasing hormone (GnRH) antagonist (Antide; administered on postnatal day, PND, 28 and 42) compared to control females and males (N = 14 per group). We predicted that, in adulthood, Antide‐treated female rats would exhibit more male‐like behaviour than control females in novel environments (elevated‐plus maze, open field and light‐dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic‐pituitary‐gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide‐treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide‐treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c‐fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long‐term effects on anxiety‐related responses in female rats.

Diverse types of genomic evidence converge on alcohol use disorder risk genes

Article

Mar 2020

Background Alcohol use disorder (AUD) is one of the most common forms of substance use disorders with a strong contribution of genetic (50%–60%) and environmental factors. Genome-wide association studies (GWAS) have identified a number of AUD-associated variants, including those in alcohol metabolism genes. These genetic variants may modulate gene expression, making individuals more susceptible to AUD. A long-term alcohol consumption can also change the transcriptome patterns of subjects via epigenetic modulations. Methods To explore the interactive effect of genetic and epigenetic factors on AUD, we conducted a secondary analysis by integrating GWAS, CNV, brain transcriptome and DNA methylation data to unravel novel AUD-associated genes/variants. We applied the mega-analysis of OR (MegaOR) method to prioritise AUD candidate genes (AUDgenes). Results We identified a consensus set of 206 AUDgenes based on the multi-omics data. We demonstrated that these AUDgenes tend to interact with each other more frequent than chance expectation. Functional annotation analysis indicated that these AUDgenes were involved in substance dependence, synaptic transmission, glial cell proliferation and enriched in neuronal and liver cells. We obtained a multidimensional evidence that AUD is a polygenic disorder influenced by both genetic and epigenetic factors as well as the interaction of them. Conclusion We characterised multidimensional evidence of genetic, epigenetic and transcriptomic data in AUD. We found that 206 AUD associated genes were highly expressed in liver, brain cerebellum, frontal cortex, hippocampus and pituitary. Our studies provides important insights into the molecular mechanism of AUD and potential target genes for AUD treatment.

Meat and Alcohol Consumption: Diet and Lifestyle Choice and Cancer

Chapter

Aug 2023

Renee Stubbins

The American Cancer Society estimates that at least 18% of all cancers and about 16% of cancer deaths in the United States of America (USA) are related to excess body weight, physical inactivity, alcohol consumption, and/or poor nutrition. A western diet has been strongly associated with an increased risk for colorectal cancer (CRC) compared to a diet that is rich in fiber from fruits, vegetables, whole grains, and lean proteins.The mechanisms that are discussed to explain the relationship between red meat and CRC include: Heme-iron in red meat, heterocyclic amines (HCAs), formation of N-glycolylneuraminic acid (Neu5Gc), polycyclic aromatic hydrocarbons (PAHs) formed when cooking meat and N-nitroso compounds (NOCs) and more recently the effects on the intestinal microbiota.It has also been established that alcohol consumption increases the risk to at least six different cancer types: breast, nasopharyngeal, mouth, laryngeal, esophageal, and colon. Yet, many Americans are unaware that alcohol consumption is associated with increased cancer risk. Alcohol is metabolized to acetaldehyde (AA), which increases the risk to carcinogenesis by directly and indirectly causing DNA damage.Our diet and lifestyle offer a unique opportunity to help reduce our risk by changing our behaviors and actions, which can be achieved by educating the public and encouraging proactive changes to health policies. Lastly, efforts should be made to create equitable access to healthy food and safe environments for all socioeconomic classes; this is an essential step in changing health policy and impacting population health and our environment.KeywordsRed meatAlcoholColorectal cancerNutritionCancer

Anti-Cancer Potential of Edible/Medicinal Mushrooms in Breast Cancer

Article

Full-text available

Jun 2023
INT J MOL SCI

Edible/medicinal mushrooms have been traditionally used in Asian countries either in the cuisine or as dietary supplements and nutraceuticals. In recent decades, they have aroused increasing attention in Europe as well, due to their health and nutritional benefits. In particular, among the different pharmacological activities reported (antibacterial, anti-inflammatory, antioxidative, antiviral, immunomodulating, antidiabetic, etc.), edible/medicinal mushrooms have been shown to exert in vitro and in vivo anticancer effects on several kinds of tumors, including breast cancer. In this article, we reviewed mushrooms showing antineoplastic activity again breast cancer cells, especially focusing on the possible bioactive compounds involved and their mechanisms of action. In particular, the following mushrooms have been considered: Agaricus bisporus, Antrodia cinnamomea, Cordyceps sinensis, Cordyceps militaris, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Lentinula edodes, and Pleurotus ostreatus. We also report insights into the relationship between dietary consumption of edible mushrooms and breast cancer risk, and the results of clinical studies and meta-analyses focusing on the effects of fungal extracts on breast cancer patients.

Alcoholic beverages and health effects

Chapter

Nov 2022

World Health Organization (WHO) Classification of Diseases reported that consumption of alcohol may impact an individual's health and increase the risk of harmful health conditions. The purpose of this chapter is to provide a general overview of the short term and long-term effects of alcohol on the body. Some of the areas that are included in this chapter are association between alcohol consumption and its effect on neurotransmitters, reproductive health, pregnancy, liver disease, cardiovascular health, nutrition, cancer, and obesity. Recent trends in treatment for alcoholism includes combination of medications, behavioral treatment, and peer support. USFDA approved drugs for treatment of alcohol dependence are disulfiram, naltrexone and acamprosate, although these treatments are not equally effective for every individual. Top investigators in this field suggest that several other factors, such as psychosocial and economic, as well as genetic variation are dependent upon interindividual variation, clinical presentation of alcohol problems and response to a given treatment. LD50 doses of ethanol are 661 mg/kg (oral) in rats, and 561 mg/kg in mouse (subcutaneous). Recent evidence regarding alcohol use disorders (AUD), fetal alcohol spectrum of disorders (FASD), and pharmacogenetic considerations are discussed in this chapter.

Diet, Lifestyle, and AGA/FPHL

Chapter

Oct 2022

Konstantinos Anastassakis

Genetic factors, androgens, and follicular micro-inflammation play key roles in causing “androgenic” hair loss (see Chaps. 11 and 14, Vol. 1) In order to affect the course and progression of AGA through diet or lifestyle, the only parameter in AGA that could be “manipulated” is the hormonal one, which includes several sub-components:Only the production and transfer steps could be modified through dietary and lifestyle changes, either towards a favorable decrease or an—unwanted—increase in overall androgen availability. The consumption of androgen-containing foods could exacerbate FPHL in some women, but it is unlikely that men would experience any detrimental effects because of high endogenous androgen levels. In the following sections, those lifestyle factors that could impact the course of AGA/FPHL, either by affecting androgen metabolism or by directly influencing the hair follicle physiology, will be examined.

Low-Dose Occupational Exposure to Nickel and Thyroid Hormones

Article

Aug 2022

Introduction: The aim of this study is to evaluate the effects of a low dose exposure to nickel, as it present in urban air, on thyroid hormones and on TSH in outdoor workers, exposed to urban pollutants. Materials and methods: 164 outdoor workers are studied and divided by gender and smoking habit. Each worker underwent measurement of urinary nickel and of blood fT3, fT4 and TSH levels. The statistical analysis was performed. Results: Statistical analysis shows a significant and positive correlation between urinary nickel and fT4, both in total sample and in males. Discussion and conclusion: The study suggests that occupational exposure to low dose of nickel may affect thyroid function in Municipal Police workers. These data may provide information on other categories of outdoor workers with similar exposure.

Thyroid Dysfunction in Patients with Liver Cirrhosis and its Association with the Severity of Liver Disease: A Cross-sectional Study

Article

Full-text available

Jul 2022

Introduction: There exists a complex relation between the thyroid hormones and liver physiology in health and disease. The liver along with the thyroid gland play a significant role in the conversion of inactive Thyroxine (T4) to active Triiodothyronine (T3). The most common thyroid hormone profile in cirrhosis of liver is a low total T3 and free T3, secondary to reduced activity of deiodinase type 1 and increased conversion to reverse Triiodothyronine (rT3). Aim: To assess the association between the thyroid hormone levels and severity of liver disease, expressed in terms of child pugh score in tertiary care hospital in Goa. Materials and Methods: This cross-sectional observational study included hundred patients with liver cirrhosis, admitted at a tertiary care hospital in Goa, from October 2019 to September 2020. The thyroid hormone levels were estimated from an early morning fasting blood sample within 24 hours of admission, once the patient satisfied the inclusion criteria. The Child Turgott Pugh scoring system was used to classify patients as per their severity of liver disease. The data was entered and analysed in Statistical Package for Social Sciences (SPSS) software version 14.0. Results: There were 95 males and 5 females. The study showed low mean levels of total T4 and free T3 in patients with cirrhosis of liver, which was significantly associated with Child Pugh classes of liver dysfunction. There was an association between levels of free T3 and the classes of Child Pugh score. The difference in the mean levels of TSH, total T3 and free T4 across the Child Pugh classes were not statistically significant. Conclusion: The study showed low free T3 levels in patients with cirrhosis of liver as seen in similar studies done in various settings. Thus, Thyroid Function Tests (TFTs) especially free T3 levels have a considerable potential to be used an independent predictor or a proxy to prognosis in patients with liver cirrhosis.

Jack "the Ripper": Fixing the Hour of His ( Probably) Last Murder

Article

Jan 2022

FACTORS THAT PROMOTE THE MAINTENANCE OF HOMEOSTASIS IN THE HUMAN BODY -A PHYSIOLOGICAL CONCEPT

Book

Full-text available

Feb 2022

Robbert Bipat

Inaugural address pronounced in abbreviated and free form at the time of acceptance of the post of professor in the Chair of Physiology with emphasis on homeostasis at the Faculty of Medical Sciences of the Anton de Kom University of Suriname on 12 January 2022. Originally published in Dutch, translated by the author 10 February 2022.

FACTOREN DIE HET BEHOUD VAN DE HOMEOSTASE IN HET MENSELIJK LICHAAM BEVORDEREN -Een fysiologisch concept

Book

Full-text available

Jan 2022

Robbert Bipat

Leerstoel Fysiologie met de nadruk op Homeostase Op 12 januari 2022 installeert de Anton de Kom Universiteit van Suriname de leerstoel Fysiologie met de nadruk op Homeostase. Ter gelegenheid daarvan zal dr. R. Bipat de inaugurele rede getiteld “Factoren die het behoud van de homeostase in het menselijk lichaam bevorderen – Een Fysiologisch Concept” houden en daarmee het hoogleraarschap in de leerstoel aanvaarden. Homeostase staat voor een constante toestand van evenwicht. In dit geval spreken we van een constant houden van fysische, chemische en biologische factoren in ons lichaam. De homeostase kan steeds verstoord worden wanneer de input of output van een van deze factoren verandert. Oorzaken voor verstoring zijn onder andere voeding, klimaatverandering, microbiële infecties en inwendige verandering van orgaanfuncties zoals van het hart, de bloedvaten, endocriene organen of uitscheidingsorganen. Zolang de verstoring kan worden gecompenseerd en de homeostase behouden blijft, is het lichaam gezond. Wanneer de compensatiemechanismen tekortschieten, worden wij ziek en kunnen bij aanhouden daarvan ook nog sterven. Voor wat betreft de voeding spelen de hoeveelheid, samenstelling en fysieke conditie van het voedsel een rol bij de verstoring van de homeostase. Klimaatverandering is een minder voor de hand liggende oorzaak voor verstoring van de homeostase. Volgens recente publicaties kan dit fenomeen leiden tot onder andere temperatuur gerelateerde ziekte en dood (zonnesteek), verandering van de microbiële samenstelling van onze darmen, verergering van aandoeningen van hart, vaten en longen en mentale stoornissen. Deze voorbeelden zijn maar enkele die de basis vormen van onderzoekslijnen die vanuit de leerstoel zullen worden uitgevoerd.

The impact of alcohol on the levels of sex hormones and risk of developing abdominal aortic aneurysm

Article

Dec 2021
J VASC SURG

Statin use and renal function after aortic aneurysm repair procedures

Article

Full-text available

Dec 2021
J VASC SURG

Medical Aspects of Drug and Alcohol Use

Chapter

Nov 2021

This extensively revised new edition provides a practical guide to understanding, assessing and managing physical, psychological and social complications related to drug and alcohol use. It presents a clear review of the aetiology, epidemiology, prevention and treatment of the problematic use of and dependence on alcohol, illicit and prescribed drugs. In doing so it strikes a balance between theory, recent research and practical clinical guidance. New chapters focus on novel psychiatric substances, smoking cessation interventions, mutual aid groups and family interventions. Written by leading specialists in the field and closely following the MRCPsych curriculum, this book is an ideal resource for trainees preparing for their RCPsych membership examinations, but is also relevant to psychiatrists at all career levels. It will also appeal to other healthcare professionals, all of whom should be able to screen for alcohol and drug use disorders, deliver brief interventions, and signpost those with more severe disorders to specialist care.

Thyroid function and IVF outcome for different indications of subfertility

Article

Full-text available

Oct 2021

Studies evaluating pregnancy outcomes after assisted reproductive treatment (ART) in women with high-normal (2.5-4.5 mIU/L) TSH levels are conflicting, possibly due to different patient charactistics and subfertility indications. The aim of this study was to examine the hypothesis that high-normal compared to low-normal TSH levels are associated with adverse implications for pregnancy outcomes in conventional in vitro fertilization (IVF)-treated women. Therefore we analysed retrospectively the characteristics and pregnancy outcomes of 949 subfertile women with TSH 0.3-4.5 mIU/L, treated with conventional IVF between January 2008 and March 2012. Demographic and baseline characteristics were compared between groups of patients based on TSH quartiles, using one-way Anova, Kruskall-Wallis ANOVA and chi-square test. Women with high-normal quartile TSH were significantly more likely to be primary subfertile (p = 0.01), with a higher prevalence of unexplained subfertility and with 15% fewer live births after IVF compared to lower TSH quartiles (p = 0.02). In secondary subfertile women with high-normal TSH male factor subfertility prevailed (p=0.01), with more live births (p=0.01). When analysing primary and secondary subfertile women as one group, these differences failed to be observed, showing no differences in cumulative pregnancy outcomes of IVF between TSH quartiles (I: 0.3-1.21 mIU/L; II: 1.22-1.68 mIU/L; III: 1.69-2.31 mIU/L; IV: 2.32-4.5 mIU/L). In conclusion, primary subfertile women predominate in the high-normal TSH quartile, associated with significantly fewer live births in a subgroup of primary unexplained subfertile women (9%; n=87/949), while in secondary subfertile women, dominated by male factor subfertility, high-normal TSH is associated with more live births.

Jumlah Sel Leydig dan Mikroanatomi Testis Tikus Putih (Rattus norvegicus) Setelah Pemberian Teh Kombucha Konsentrasi 50% Waktu Fermentasi 6, 9 dan 12 Hari

Article

Full-text available

Apr 2020

Tujuan penelitian ini untuk mengkaji potensi teh Kombucha kadar 50% dengan variasi waktu fermentasi dalam mempengaruhi jumlah sel leydig dan struktur mikroanatomi testis tikus putih (Rattus norvegicus). Penelitian ini menggunakan Tikus putih jantan sebanyak 16 ekor umur 2 bulan, dengan perlakuan Teh kombucha yang difermentasi selama 6, 9 dan 12 hari pada suhu 25oC per oral. Penelitian ini menggunakan Rancangan Acak Lengkap dengan 4 perlakuan (selama 28 hari) dan 4 ulangan, yaitu : P0 = kontrol, tanpa tambahan teh kombucha, P1 = air minum + 1,8 ml teh kombucha pagi dan sore fermentasi 6 hari, P2 = air minum + 1,8 ml teh kombucha pagi dan sore fermentasi 9 hari, P3 = air minum + 1,8 ml teh kombucha pagi dan sore fermentasi 12 hari. Variabel yang diukur adalah diameter tubulus seminiferus dan jumlah sel Leydig. Data yang diperoleh dianalisis menggunakan ANOVA yang dilanjutkan dengan Uji Duncan dengan taraf kepercayaan 95% dengan menggunakan perangkat lunak SPSS 16.0. Penelitian ini menunjukkan bahwa pemberian teh kombucha fermentasi 6, 9, dan 12 hari menurunkan diameter tubulus seminiferus sehingga berpotensi mengganggu proses spermatogenesis, tetapi tidak mempengaruhi jumlah sel Leydig tikus putih (Rattus norvegicus). Kata kunci: Rattus norvegicus, teh kombucha , tubulus seminiferus, sel leydig

More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels

Article

Full-text available

Aug 2021
GYNECOL OBSTET INVES

Objectives: The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. Design: This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22-45 years with TSH 0.3-4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and χ2 test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The χ2 test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. Results: Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. Limitations: Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. Conclusions: The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.

Olive polyphenols and chronic alcohol protection

Chapter

Jan 2021

Alcohol addiction represents a chronic condition characterized by behavioral, physical, and mental alterations, caused by compulsive consumption of high quantities of alcohol. The effects of alcoholism heavily interfere with physical health and with relational and social life. Scientific research has constantly focused on finding solutions not only for the management of psychological dependence but also for the treatment of the numerous pathologies resulting from the abuse of alcohol, including cirrhosis of the liver, chronic pancreatitis, epilepsy, polyneuropathy, heart disease, nutritional deficiencies, and neuro-behavioral problems. These alterations are generally associated with the oxidation process of alcohol and more particularly with the oxidative stress resulting in the production of free radicals and lipid peroxidation. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with neurological and physical decline, opening new avenues for its prevention. Diet, in particular, has become the object of intense research in relation to central nervous system disorders. A large body of evidence supports the beneficial effects of the Mediterranean diet in preventing degeneration at different levels. In particular, regular consumption of extra-virgin olive oil, containing natural polyphenols (tyrosol, hydroxytyrosol, and oleuropein) seems to be responsible, at least in part, for the beneficial effects of the Mediterranean diet. Polyphenols strongly show antioxidant activity, decreasing the level of reactive oxygen species in the human body. Furthermore, the health-promoting properties of plant polyphenols comprise antiinflammatory, antiallergic, antiatherogenic, antithrombotic, and antimutagenic effects. In this chapter, we aim at illustrating an overview of the recent advances in the link between polyphenols and alcohol addiction, supporting the preventive role of their consumption for alcohol-related disorders.

Alcohol: the role in nutrition and health

Chapter

Jan 2020

Paolo M. Suter

Alcohol is globally a major component of daily life and nutrition. Presently, about 61% of US adults are current drinkers. Due to its metabolic characteristics, alcohol as a function of the absolute amount consumed, consumption frequency, genetic factors etc., has a high potential to affect most metabolic pathways and cell and organ function including the metabolism and nutriture of all macro- and micronutrients. In this chapter, the present knowledge of the effects of alcohol on selected nutrients as well as health and disease burden will be summarized.

Effect of fluoride on endocrine tissues and their secretory functions - review

Article

Jul 2020
CHEMOSPHERE

The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.

The Effect of Herbicide Metribuzin on Environment and Human: A Systematic Review

Article

Jul 2020

Metribuzin is a synthetic organic compound used as a selective Triazinone herbicide, incorporated as a post-emergent soil applied herbicide to control weeds in wheat, potato, tomato and others. The aim of this study was to assess the impact of Metribuzin on the environment and human health. Human exposure to Metribuzin occurs through inhalation and ingestion, usually in agricultural settings. Farmers' occupational exposure to Metribuzin is highly variable and complex depending on the farm but Few studies have assessed the exposure of the population to this herbicide. Metribuzin can accumulate in soil and water and cause damage to flora and fauna. furthermore, Herbicides Metribuzin have a very variable toxicity, in the short term it can cause acute intoxication which can cause breathing and difficult drowsiness but the high exposures can cause stomach aches, fatigue and depression of the central nervous system, on the other hand in the long term and with strong exposure or other repeated it can cause modifications of the hepatic enzymes, disturbance in the kidneys, can affect the reproduction, the endocrine function and oxidant/antioxidant system imbalance. This study highlights on the undesirable effect of Metribuzin which allows to affirm their toxicity even at low doses, is not only following an occupational exposure, but also for the general population by their use of treated agricultural products by these pesticides, which poses a real public health problem. Accordingly, it is imperative that farmers avoid their use and replace them with biological fertilizers that are less harmful to human and animal health.

Light Alcohol Drinking and the Risk of Cancer Development: A Controversial Relationship

Article

Jun 2020

Background In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12,5g per day) is still unknown. Objective To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset. Method To collect the scientific evidences regarding this topic the keywords “light alcohol drinking”, “light alcohol consumption” and “cancer”, were used. We decided to analyze papers published during the last 15 years, in order to select the most recent evidence. Meta-analysis with well defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded. Results Twenty-nine large meta-analysis were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Furthermore, a possible protective role of light alcohol assumption consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was shown. Conclusion Light alcohol drinking was not associated to the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.

Prevention of Male Infertility: From Childhood to Adulthood

Chapter

Apr 2020

Alberto Ferlin

Male and Sperm Factors that Maximize IVF Success - edited by John Aitken April 2020

the effects of alcohol on the hormonal status of postmenopausal women

Article

Full-text available

Jan 1994
Alcohol Health Res World

Menopause is associated with increased risk for certain diseases. By affecting hormone levels, alcohol consumption might influence the occurrence or progress of these diseases.

Association of PER2 Genotype and Stressful Life Events with Alcohol Drinking in Young Adults

Article

Full-text available

Mar 2013
PLOS ONE

Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking. Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview. Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress. These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.

A prospective, case-control study on the lipid profile and the cardiovascular risk of menopausal women on oestrogen plus progestogen therapy in a northern Italy province

Article

Full-text available

Jan 2013
ARCH GYNECOL OBSTET

Purpose: To evaluate the effects of oestrogen plus progestogen therapy (EPT) on the lipid metabolism of menopausal patients. Methods: We conducted a prospective study on 223 patients with clinical and blood chemistry diagnosis of menopause, who were eligible for hormone therapy and a follow-up period lasting at least 5 years. We selected a control group. Patients attended annual or 6-monthly visits for the duration of the 5-year follow-up period. For each patient, total-cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride values were considered at the first visit and after 5 years. We compared these values of the above parameters in relation to time and EPT and the repercussions that the presence/absence of replacement therapy had in terms of lipid profile alteration between the groups studied. Results: Of the 223 patients eligible for enrolment, 178 made up the study group (EPT Group) and 45 made up the control cohort (N-EPT-Group). At the first visit, median value was (EPT-Group vs. N-EPT-Group): cholesterol was 240 versus 226 mg/dL, LDL-cholesterol 169 versus 174 mg/dL, HDL-cholesterol 60 mg/dL in both groups, triglyceride 125 versus 92 mg/dL (p:n.s). Five years later, median value was (EPT-Group versus N-EPT-Group): cholesterol 225 versus 236 mg/dL (p < 0.001), LDL-cholesterol 125 versus 184 mg/dL (p < 0.001), HDL-cholesterol 64 versus 68 mg/dL (p:n.s.), triglyceride 72 versus 94 mg/dL (p:n.s.). No adverse effects of EPT were observed. Conclusions: Thorough risk/benefit assessment, associated with initially low doses and without rigid cutoffs, particularly when started early, EPT can be made a valid means of cardiovascular prevention, specifically because it positively alters the lipid profile of menopausal women.

Circadian Genes, the Stress Axis, and Alcoholism

Article

Full-text available

Mar 2012

Dipak Sarkar

The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women

Article

Full-text available

Aug 2012
DIABETOLOGIA

Aims/hypothesis: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes with a stronger effect in women. As the underlying mechanisms remain poorly characterised, we investigated its relationship with insulin resistance, insulin secretion, clearance of insulin and glucagon concentration. Methods: One-thousand two-hundred and seventy-six non-diabetic individuals from the RISC (relationship between insulin sensitivity and cardiovascular disease) study without high alcohol consumption were studied; all had a euglycaemic-hyperinsulinaemic clamp and an OGTT with assessment of insulin sensitivity, secretion and clearance. Results: Alcohol consumption was positively associated with insulin sensitivity in women (β = 0.15, p ( trend ) = 0.005) and in men (β = 0.07, p ( trend ) = 0.07) after controlling for age, centre, waist, smoking and physical activity. In women, this association persisted after adjustment for adiponectin but was attenuated after controlling for HDL-cholesterol, suggesting that part of the protection is related to a higher HDL-cholesterol concentration. Higher alcohol consumption was associated with lower basal insulin secretion in women only (β = -0.10, p ( trend ) = 0.004) and this association persisted after adjustment for insulin sensitivity. In men, increasing alcohol consumption was associated with enhanced insulin clearance and increased fasting NEFA concentrations, independently of insulin sensitivity. Fasting glucagon decreased with increasing alcohol in women only (abstainers 9.2 ± 4.4; <28 g/week 8.6 ± 4.0; 28-64 g/week 8.1 ± 3.7; >64 g/week 7.5 ± 3.1 pmol/l; p ( trend ) = 0.01). Conclusions/interpretation: Light-to-moderate alcohol consumption was associated in healthy women with enhanced insulin sensitivity, reduced basal insulin secretion rate and lower fasting plasma glucagon concentration, providing consistent mechanisms for the reduced risk of diabetes.

A promoter polymorphism in the Per3 gene is associated with alcohol and stress response

Article

Full-text available

Feb 2012

The period homolog genes Per1, Per2 and Per3 are important components of the circadian clock system. In addition to their role in maintaining circadian rhythm, these genes have been linked to mood disorders, stress response and vulnerability to addiction and alcoholism. In this study, we combined high-resolution sequence analysis and quantitative trait locus (QTL) mapping of gene expression and behavioral traits to identify Per3 as a compelling candidate for the interaction between circadian rhythm, alcohol and stress response. In the BXD family of mouse strains, sequence variants in Per3 have marked effects on steady-state mRNA and protein levels. As a result, the transcript maps as a cis-acting expression QTL (eQTL). We found that an insertion/deletion (indel) variant in a putative stress response element in the promoter region of Per3 causes local control of transcript abundance. This indel results in differences in protein binding affinities between the two alleles through the Nrf2 transcriptional activator. Variation in Per3 is also associated with downstream differences in the expression of genes involved in circadian rhythm, alcohol, stress response and schizophrenia. We found that the Per3 locus is linked to stress/anxiety traits, and that the basal expression of Per3 is also correlated with several anxiety and addiction-related phenotypes. Treatment with alcohol results in increased expression of Per3 in the hippocampus, and this effect interacts with acute restraint stress. Our data provide strong evidence that variation in the Per3 transcript is causally associated with and also responsive to stress and alcohol.

Chronic Shift-Lag Alters the Circadian Clock of NK Cells and Promotes Lung Cancer Growth in Rats

Article

Full-text available

Mar 2012
J IMMUNOL

Prolonged subjection to unstable work or lighting schedules, particularly in rotating shift-workers, is associated with an increased risk of immune-related diseases, including several cancers. Consequences of chronic circadian disruption may also extend to the innate immune system to promote cancer growth, as NK cell function is modulated by circadian mechanisms and plays a key role in lysis of tumor cells. To determine if NK cell function is disrupted by a model of human shift-work and jet-lag, Fischer (344) rats were exposed to either a standard 12:12 light-dark cycle or a chronic shift-lag paradigm consisting of 10 repeated 6-h photic advances occurring every 2 d, followed by 5-7 d of constant darkness. This model resulted in considerable circadian disruption, as assessed by circadian running-wheel activity. NK cells were enriched from control and shifted animals, and gene, protein, and cytolytic activity assays were performed. Chronic shift-lag altered the circadian expression of clock genes, Per2 and Bmal1, and cytolytic factors, perforin and granzyme B, as well as the cytokine, IFN-γ. These alterations were correlated with suppressed circadian expression of NK cytolytic activity. Further, chronic shift-lag attenuated NK cell cytolytic activity under stimulated in vivo conditions, and promoted lung tumor growth following i.v. injection of MADB106 tumor cells. Together, these findings suggest chronic circadian disruption promotes tumor growth by altering the circadian rhythms of NK cell function.

Alcohol consumption and total estradiol in premenopausal women

Article

Full-text available

Mar 1998

The present paper analyzes the relation between alcohol intake and serum total estradiol in premenopausal women while attempting to control or reduce several sources of variability of serum estradiol. Sixty premenopausal women were recruited, and alcohol intake was estimated by a semiquantitative questionnaire. Interviews, anthropometric measurements, and blood drawings (after overnight fasting) were conducted twice, 1 year apart. Both blood samples were obtained on the same day of the luteal phase of the cycle, in the same month and in the same hour and minute of the day. Samples from the first drawing were stored at -80 degrees C. Serum from both drawings was assayed simultaneously and in blind fashion. A significant association between alcohol intake and estradiol was found when estradiol was averaged across the two visits (Spearman's r = 0.29; P < 0.05). To control for intraindividual variability of estradiol over time, participants were then divided into tertiles of hormone distribution for each of the two sets of measurements and classified based on their consistency in estradiol across the two visits. Women showing consistently high estradiol levels at both visits were characterized by a significantly higher alcohol intake (92.8 g/week) in comparison with those showing consistently low estradiol at both visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with consistently high estradiol was significantly higher than in the group with consistently low estradiol. The present report indicates that drinkers seem to be characterized by consistently higher estradiol than nondrinkers, and that when the variability of estradiol in premenopause is considered, it is possible to identify a relationship between alcohol intake and estradiol.

Chronic Ethanol Consumption-induced Pancreatic -Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Article

Full-text available

Nov 2010
J BIOL CHEM

Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of chronic ethanol consumption on pancreatic β-cell dysfunction and whether generated peroxynitrite participates in the impaired glucose homeostasis. Here we show that chronic ethanol feeding decreases the ability of pancreatic β-cells to mediate insulin secretion and ATP production in coordination with the decrease of glucokinase, Glut2, and insulin expression. Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(ΔC) attenuated ethanol-induced pancreatic β-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol. GCK inactivation and down-regulation were predominantly mediated by ethanol metabolism-generated peroxynitrite, which were suppressed by the peroxynitrite scavengers N(γ)-monomethyl-L-arginine, uric acid, and deferoxamine but not by the S-nitrosylation inhibitor DTT, indicating that tyrosine nitration is the predominant modification associated with GCK down-regulation and inactivation rather than S-nitrosylation of cysteine. Tyrosine nitration of GCK prevented its association with pBad, and GCK translocation into the mitochondria results in subsequent proteasomal degradation of GCK following ubiquitination. This study identified a novel and efficient pathway by which chronic ethanol consumption may induce GCK down-regulation and inactivation by inducing tyrosine nitration of GCK, resulting in pancreatic β-cell apoptosis and dysfunction. Peroxynitrite-induced ATF3 may also serve as a potent upstream regulator of GCK down-regulation and β-cell apoptosis.

Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development

Article

Full-text available

Mar 2010
WORLD J GASTROENTERO

Chronic inflammation is often associated with alcohol-related medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.

New Concepts on the Control of the Onset of Puberty

Article

Full-text available

Jan 2010

The initiation of mammalian puberty requires an increased pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This increase is brought about by changes in transsynaptic and glial-neuronal communication. Coordination of these cellular interactions likely requires the participation of sets of genes hierarchically arranged within functionally connected networks. Using high throughput, genetic, molecular and bioinformatics strategies, in combination with a systems biology approach, three transcriptional regulators of the pubertal process have been identified, and the structure of at least one hypothalamic gene network has been proposed. A genomewide analysis of hypothalamic DNA methylation revealed profound changes in methylation patterns associated with the onset of female puberty. Pharmacological disruption of two epigenetic marks associated with gene silencing (DNA methylation and histone deacetylation) resulted in pubertal failure, instead of advancing the onset of puberty, suggesting that disruption of these two silencing mechanisms leads to activation of repressor genes whose expression would normally decrease at puberty. These observations suggest that the genetic underpinnings of puberty are polygenic rather than specified by a single gene, and that epigenetic mechanisms may provide coordination and transcriptional plasticity to this genetic network.

Critical Role of TLR4 Response in the Activation of Microglia Induced by Ethanol

Article

Full-text available

Oct 2009
J IMMUNOL

Microglial cells are the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes associated with a variety of neurological and pathological disorders. Alcohol consumption induces brain damage, although the neuropathological processes are poorly understood. We previously suggested that ethanol promotes inflammatory processes in the brain, up-regulating inflammatory mediators and signaling pathways associated with IL-1RI/TLR4 receptors. In the present study we investigate whether ethanol induces microglia activation by stimulating TLR4 response and whether this response causes neuronal death and contributes to ethanol-induced neuroinflammatory damage. We demonstrate that ethanol activates microglía and stimulates NF-kappaB, MAPKs, and MyD88-independent (IFN regulatory factor-3, IFN-beta) pathways to trigger the production of inflammatory mediators, causing neuronal death. The inflammatory response induced by ethanol is completely abrogated in microglia of TLR4-deficient mice (TLR4(-/-)), thus supporting the role of these receptors in microglia activation and neuronal death. In accord with the in vitro findings, acute ethanol administration induces microglia activation (CD11b(+) cells) in cerebral cortex of TLR4(+/+) mice, but not in TLR4(-/-) mice. Taken together, our results not only provide the first evidence of the critical role of the TLR4 response in the ethanol-induced microglia activation, but also new insight into the basic mechanisms participating in ethanol-induced neuroinflammatory damage.

Functional CRH variation increases stress-induced alcohol consumption in primates

Article

Full-text available

Sep 2009
P NATL ACAD SCI USA

Corticotropin-releasing factor (CRF), encoded by the CRH gene, is a key integrator of stress responses, and, as such, CRH gene variation may contribute to individual differences in susceptibility to stress-related pathology. In rhesus macaques, a single nucleotide polymorphism (SNP) is found within the CRH promoter (-248C--> T). Here, we assessed whether this variant influenced stress responding and, because increased CRF system activity drives alcohol drinking in rodents, we examined whether it predicted voluntary alcohol consumption as a function of prior stress exposure. Using a hypothalamic nuclear extract, we showed that the -248 T allele resulted in increased DNA protein interactions relative to the C allele. In vitro, the T allele resulted in CRH promoter activity that was higher following both stimulation with forskolin and treatment with dexamethasone. Endocrine and behavioral responses to social separation stress (release of ACTH and cortisol, and suppression of environmental exploration, respectively) were higher among carriers of the T allele, particularly among those exposed to early adversity in the form of peer rearing. We also found that T allele carriers with a history of early life adversity consumed more alcohol in a limited-access paradigm. Our data suggest that CRH promoter variation that confers increased stress reactivity increases the risk for alcohol use disorders in stress-exposed individuals.

Alcohol Abuse, Immunosuppression, and Pulmonary Infection

Article

Full-text available

Feb 2008

Excessive alcohol consumption predisposes the host to a wide range of infectious complications, particularly pulmonary infections. Factors that contribute to the development of pulmonary infections in alcohol-abusing patients include dysfunction of the protective barriers in the respiratory tract, aspiration of oropharyngeal contents, nutritional deficiencies, liver disease, and impairment of host defense mechanisms. This review discusses the complex host-pathogen interactions in the airways with an emphasis on how alcohol consumption adversely affects these mechanisms and predisposes the host to infections. Potential immunomodulatory strategies for enhancing host defense function in alcohol-consuming patients are also discussed.

The Opposite Effects of Acute and Chronic Alcohol on Lipopolysaccharide-Induced Inflammation Are Linked to IRAK-M in Human Monocytes

Article

Full-text available

Jul 2009
J IMMUNOL

Impaired host defense after alcohol use is linked to altered cytokine production, however, acute and chronic alcohol differently modulate monocyte/macrophage activation. We hypothesized that in human monocytes, acute alcohol induces hyporesponsiveness to LPS, resulting in decreased TNF-alpha, whereas chronic alcohol increases TNF-alpha by sensitization to LPS. We found that acute alcohol increased IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of IRAK-1, in human monocytes. This was associated with decreased IkappaB alpha kinase activity, NFkappaB DNA binding, and NFkappaB-driven reporter activity after LPS stimulation. In contrast, chronic alcohol decreased IRAK-M expression but increased IRAK-1 and IKK kinase activities, NFkappaB DNA binding, and NFkappaB-reporter activity. Inhibition of IRAK-M in acute alcohol-exposed monocytes using small interfering RNA restored the LPS-induced TNF-alpha production whereas over-expression of IRAK-M in chronic alcohol macrophages prevented the increase in TNF-alpha production. Addition of inhibitors of alcohol metabolism did not alter LPS signaling and TNF-alpha production during chronic alcohol exposure. IRAK-1 activation induces MAPKs that play an important role in TNF-alpha induction. We determined that acute alcohol decreased but chronic alcohol increased activation of ERK in monocytes and ERK inhibitor, PD98059, prevented the chronic alcohol-induced increase in TNF-alpha. In summary, inhibition of LPS-induced NFkappaB and ERK activation by acute alcohol leads to hyporesponsiveness of monocytes to LPS due to increased IRAK-M. In contrast, chronic alcohol sensitizes monocytes to LPS through decreased IRAK-M expression and activation of NFkappaB and ERK kinases. Our data indicate that IRAK-M is a central player in the opposite regulation of LPS signaling by different lengths of alcohol exposure in monocytes.

Effects of Growth Hormone on Glucose, Lipid, and Protein Metabolism in Human Subjects

Article

Full-text available

Mar 2009
ENDOCR REV

In evolutionary terms, GH and intracellular STAT 5 signaling is a very old regulatory system. Whereas insulin dominates periprandially, GH may be viewed as the primary anabolic hormone during stress and fasting. GH exerts anabolic effects directly and through stimulation of IGF-I, insulin, and free fatty acids (FFA). When subjects are well nourished, the GH-induced stimulation of IGF-I and insulin is important for anabolic storage and growth of lean body mass (LBM), adipose tissue, and glycogen reserves. During fasting and other catabolic states, GH predominantly stimulates the release and oxidation of FFA, which leads to decreased glucose and protein oxidation and preservation of LBM and glycogen stores. The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels. In the basal state, the effects of GH on protein metabolism are modest and include increased protein synthesis and decreased breakdown at the whole body level and in muscle together with decreased amino acid degradation/oxidation and decreased hepatic urea formation. During fasting and stress, the effects of GH on protein metabolism become more pronounced; lack of GH during fasting increases protein loss and urea production rates by approximately 50%, with a similar increase in muscle protein breakdown. GH is a counterregulatory hormone that antagonizes the hepatic and peripheral effects of insulin on glucose metabolism via mechanisms involving the concomitant increase in FFA flux and uptake. This ability of GH to induce insulin resistance is significant for the defense against hypoglycemia, for the development of "stress" diabetes during fasting and inflammatory illness, and perhaps for the "Dawn" phenomenon (the increase in insulin requirements in the early morning hours). Adult patients with GH deficiency are insulin resistant-probably related to increased adiposity, reduced LBM, and impaired physical performance-which temporarily worsens when GH treatment is initiated. Conversely, despite increased LBM and decreased fat mass, patients with acromegaly are consistently insulin resistant and become more sensitive after appropriate treatment.

Interaction of ethanol with signal transduction mechanisms mediating growth hormone release by rat pituitary cells in vitro.

Article

Jul 1992

The effects of ethanol on signal transduction mechanisms of rat GH (rGH) release were investigated in primary culture of rat anterior pituitary cells. Ethanol (30, 100, and 300 mM) had no significant effect on basal rGH release or cell content after a 4-h incubation or on intracellular cAMP levels at 30 min. Ethanol did not alter rGRH (10(-11) M)-stimulated rGH release, but at concentrations of 100 and 300 mM it inhibited rGRH (10(-9) M)-stimulated rGH release by 12% (P less than 0.05) and 54% (P less than 0.01). In contrast, a dose-dependent stimulatory effect was observed on rGRH-induced cAMP accumulation. Ethanol enhanced the inhibitory effect of SRIH (10(-11) and 10(-9) M) on rGH release by up to 24% (P less than 0.01). Stimulation of rGH release by cAMP derivatives and forskolin was partially inhibited by ethanol, as was cAMP accumulation after forskolin treatment. Cholera toxin-stimulated rGH release was also inhibited by ethanol, whereas cAMP accumulation was increased. At the higher concentrations, ethanol enhanced rGH release after protein kinase-C activation by phorbol ester and after stimulation of calcium influx with Ca ionophore. No significant ethanol effect was noted on prostaglandin E2-stimulated rGH release, and ethanol did not alter rGH mRNA levels or proliferation of a pituitary somatomammotroph cell line. The results indicate that ethanol exerts multiple effects on systems mediating GH release from the pituitary in vitro. However, the inhibitory influence of ethanol on GH secretion is related primarily to the adenylate cyclase-cAMP pathway, which represents the major signal transducing system in the somatotroph.

The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991-1992 and 2001-2002

Article

Jan 2004
DRUG ALCOHOL DEPEN

Effects on pubertal hormones by ethanol abuse in adolescents

Article

Jan 1993

Drug abuse: Hedonic homeostatic dysregulation

Article

Oct 1997

Understanding the neurobiological mechanisms of addiction requires an integration of basic neuroscience with social psychology, experimental psychology, and psychiatry. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug-taking. Sensitization and counteradaptation are hypothesized to contribute to this hedonic homeostatic dysregulation, and the neurobiological mechanisms involved, such as the mesolimbic dopamine system, opioid peptidergic systems, and brain and hormonal stress systems, are beginning to be characterized. This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.

Stress and Neuroendocrine-Immune Interaction: A Therapeutic Role for β-endorphin

Chapter

Nov 2013

This chapter focuses on the neuroendocrine response to stress and its potential to be programmed by early-life events. Regardless of the source of the stress, the same physiological response occurs: the hypothalamic—pituitary—adrenal (HPA) axis initiates a reliable hormonal cascade that results in glucocorticoids (GC) being released into circulation. Studies investigating postnatal stressors in animals use either models of neonatal infection or maternal deprivation. Any period of significant growth and development is vulnerable to the detrimental effects of stress. The focus of much research is the prenatal period, while less is known about the effects of stress during adolescence. The HPA axis and sympathetic nervous system are major pathways by which the brain regulates immune processes. The peptide, β-endorphin (BEP), is known to have the ability to inhibit stress hormone production, produce analgesia and promote a feeling of wellbeing.

A good public debate

Article

Apr 1996

Alcohol intake induces diminished ovarian reserve in childbearing age women

Article

Feb 2013
J OBSTET GYNAECOL RE

Aim: To investigate the adverse effects of alcohol on ovarian reserve in women of childbearing age. Material and methods: Twenty bar hostesses between the ages of 18 and 29 with moderate alcohol consumption for over 3 years and 16 healthy women between the ages of 18 and 28 with alcohol consumption under a healthy standard were recruited. Their ovarian reserve was evaluated by measuring menstrual cycle day three (CD3) serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL) and testosterone (TST) levels, and by transvaginal B-ultrasound examination of uterine size, ovarian size and number of antral follicles. Results: Moderate consumption of alcohol significantly increased serum FSH level (P=0.001), but had no effect on serum LH, E2, PRL and TST levels. Moderate alcohol consumption significantly decreased ovarian volume (P=0.000) and number of ovarian antral follicles (P=0.015), but had no effect on uterus size. Moderate alcohol consumption significantly increased the occurrence of menstrual flow abnormalities (P=0.001 and P=0.036, respectively), but had no effect on menstrual cycle. The amount of alcohol consumed positively correlated with FSH, and negatively correlated with ovarian volume and number of antral follicles in women with moderate alcohol consumption. Conclusion: Long-term moderate alcohol consumption may lead to diminished ovarian reserve.

Horloge endogène et consommation d’alcool: The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption

Article

Jan 2006

Relations among stress, Coping strategies, Coping motives, Alcohol consumption and related problems: A mediated moderation model

Article

Dec 2012

Although prominent models of alcohol use and abuse implicate stress as an important motivator of alcohol consumption, research has not consistently identified a relationship between stress and drinking outcomes. Presumably stress leads to heavier alcohol consumption and related problems primarily for individuals who lack other adaptive methods for coping effectively with stressful experiences. To test this hypothesis, we examined four adaptive coping approaches (active coping, planning, suppression of competing activities, and restraint), as predictors of alcohol use and related problems as well as moderators of relations between stress and drinking outcomes in an undergraduate population (N=225). Further, we examined coping motives for drinking as potential mediators of the effects of coping strategies as well as stress by coping strategy interactions. Analyses supported both restraint and suppression of competing activities as moderators of the influence of stress on alcohol use but not problems. The stress by restraint interaction was also evident in the prediction of coping motives, and coping motives were related to higher levels of both weekly drinking and alcohol-related problems. Finally, coping motives for drinking served to mediate the stress by restraint interaction on weekly drinking. Overall, these results suggest that efforts to suppress competing activities and restrain impulsive responses in the face of stress may reduce the risk for heavy drinking during the transition from high school to college.

Biochemical mechanisms that contribute to alcohol-induced hypogonadism in the male

Article

Feb 2008
ALCOHOL CLIN EXP RES

An overview of the biochemical mechanisms known to contribute to alcoholinduced Leydig cell failure is presented, along with results of studies performed both in vitro and in vivo. The data obtained in animals and in various in vitro model systems is discussed in terms of its application to the clinical situation.

Minireview: The Neural Regulation of the Hypothalamic-Pituitary-Thyroid Axis

Article

Jul 2012
ENDOCRINOLOGY

Thyroid hormone (TH) signaling plays an important role in development and adult life. Many organisms may have evolved under selective pressure of exogenous TH, suggesting that thyroid hormone signaling is phylogenetically older than the systems that regulate their synthesis. Therefore, the negative feedback system by TH itself was probably the first mechanism of regulation of circulating TH levels. In humans and other vertebrates, it is well known that TH negatively regulates its own production through central actions that modulate the hypothalamic-pituitary-thyroid (HPT) axis. Indeed, primary hypothyroidism leads to the up-regulation of the genes encoding many key players in the HPT axis, such as TRH, type 2 deiodinase (dio2), pyroglutamyl peptidase II (PPII), TRH receptor 1 (TRHR1), and the TSH α- and β-subunits. However, in many physiological circumstances, the activity of the HPT axis is not always a function of circulating TH concentrations. Indeed, circadian changes in the HPT axis activity are not a consequence of oscillation in circulating TH levels. Similarly, during reduced food availability, several components of the HPT axis are down-regulated even in the presence of lower circulating TH levels, suggesting the presence of a regulatory pathway hierarchically higher than the feedback system. This minireview discusses the neural regulation of the HPT axis, focusing on both TH-dependent and -independent pathways and their potential integration.

Ethanol‐induced alterations in the morphology and function of the rat ovary

Article

Feb 1982
Anat Rec

The purpose of this study was to compare the effects of different dosages of ethanol on ovarian morphology and function. Holtzman rats, 20 days old, were divided into groups as follows: The rats in Group I were autopsied at 20 days of age, and those in Group II were placed on ad libitum chow and water diet; the rats in Groups III and V were fed on a liquid diet containing 2.5% or 5% ethanol respectively; Groups IV and VI were pair-fed controls to Groups III and V, respectively. Rats in Groups II, III, IV, and VI were maintained on the diets for 50–55 days and killed at late proestrus-estrus, while the animals in Group V did not exhibit estrous cycles and were killed on day 55 of treatment. The average increase in body weights of rats in Groups II, III, and IV was significantly greater than the increase in body weights of rats given 5% ethanol or their pair-fed controls. In the rats treated with 5% ethanol, vaginal opening was significantly delayed from the controls, estrous cycles were absent, ovarian weights were similar to those of the 20-day-old rats, ovaries contained corpora lutea of only one estrus, uteri weighed less than controls, and histologically, the uteri and vaginae were similar to those of 20-day-old rats. However, in the rats treated with 2.5% ethanol, all of the parameters were similar to those of the controls. The average serum alcohol level for the rats on the 5% ethanol diet was 249 mg%; the serum alcohol levels were at the lower limit of detection for the rats on the 2.5% ethanol diet. The data show that ovarian function was suppressed in the rats that received the 5% ethanol but not in rats on the 2.5% ethanol diet.

Adrenocortical Responses and Family History of Alcoholism

Article

Jul 1999
ALCOHOL CLIN EXP RES

Background: This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered hypothalamic-pituitary-adrenal (HPA) axis dynamics compared with nonalcoholic subjects without a family history of alcohol dependence. Methods: Seventy-eight nonalcoholic subjects aged 18 to 25 were enrolled in the protocol. Thirty-nine subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive (FHP) subjects. Thirty-nine subjects were biological offspring of nonalcohol-dependent parents and were designated as family history-negative (FHN) subjects. Subjects received naloxone hydrochloride (0 and 125 μg/kg) and cosyntropin (0, 0.25 μg, and 250 μg) in double-blind, randomized order and Cortisol was monitored. A subset of subjects (11 FHP, 11 FHN) was admitted to the General Clinical Research Center to measure serum Cortisol levels every 30 min for 24 hr. Results: FHP subjects had an increased Cortisol response to opioid receptor blockade induced by naloxone. However, no group differences in Cortisol were uncovered during administration of cosyntropin or during monitoring of the Cortisol circadian profile. Conclusion: These observations suggest that differences in the Cortisol dynamics between FHP and FHN subjects are unmasked by opioid receptor blockade directed at the hypothalamus, but not when Cortisol levels are directly provoked at the level of the adrenal gland. In addition, unprovoked Cortisol secretion monitored over a 24-hr interval cannot distinguish FHP from FHN subjects.

Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state

Article

Oct 2008
EUR J NEUROSCI

Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ‘low-responding’ non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ∼0.4 mg/kg/session), and most blunted in dependent animals (averaging ∼1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.

Chronic Daily Ethanol and Withdrawal: 1. Long‐Term Changes in the Hypothalamo‐Pituitary‐Adrenal Axis

Article

Dec 2000
ALCOHOL CLIN EXP RES

Background: Hypothalamo-pituitary-adrenal (HPA) function has been demonstrated to be compromised for weeks and even months after alcoholics cease ethanol consumption. Because nonalcoholic subjects with family history-associated increased risk for alcoholism also exhibit compromised HPA function, it is not clear whether defects in the HPA axis of abstinent alcoholics reflect a preexisting condition that may be responsible for increased risk for alcohol abuse versus a persisting adaptational change in response to prolonged alcohol abuse. Consequently, we investigated whether chronic daily ethanol consumption and withdrawal by male Sprague Dawley® rats would induce persistent HPA changes consistent with those demonstrated in abstinent alcoholics.

Frontal Lobe Volume Loss Observed with Magnetic Resonance Imaging in Older Chronic Alcoholics

Article

May 1997
ALCOHOL CLIN EXP RES

This study used magnetic resonance imaging to quantify the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in younger versus older chronic alcoholics relative to normal controls. In the present analysis, we divided our previously reported group of 62 alcoholic men into a younger group (n = 33, age mean = 37.5 ± 4.5, and range = 26 to 44 years) and an older group (n= 29, age mean = 52.7 ± 6.0, and range = 45 to 63 years) to examine whether, in addition to extent, the two age groups differed in pattern of tissue type and regional brain volume abnormalities quantified with magnetic resonance imaging. Brain volumes were adjusted for normal variation in head size and age established from a group of healthy controls and were expressed as Z-scores. The younger group had significant cortical gray, but not white, matter volume deficits and sulcal and ventricular enlargement relative to age-matched controls. The older group had volume deficits in both cortical gray and white matter and sulcal and ventricular enlargement that significantly exceeded the younger alcoholic group. An analysis of six cortical regions revealed that, although both age groups had gray matter volume deficits throughout the cortex, the older alcoholic group had a selectively more severe deficit in prefrontal gray matter relative to the younger alcoholic group. Similarly, the cortical white matter volume deficit in the older alcoholics was especially severe in the prefrontal and frontal regions. The differences in brain dysmorphology between the two alcoholic groups cannot easily be attributed to potential alcohol history differences typically related to age because the two groups had similar disease durations and amounts of lifetime alcohol consumption. These results provide in vivo evidence that the frontal lobes are especially vulnerable to chronic alcoholism in older men.

Effects of ethanol on pancreatic beta-cell death: Interaction with glucose and fatty acids

Article

Apr 2009

Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic β-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on β-cell survival and metabolism. We treated the rat β-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen species (ROS) were determined by (5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst 33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and affect mitochondrial function in RINm5F β-cells. However, ethanol causes β-cell death by apoptosis, whereas fatty acids cause cell death predominantly by necrosis. It is not known whether these results are applicable to human β-cells.

Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats

Article

Aug 1994
PHARMACOL BIOCHEM BE

The fluid intake of male Wistar rats with simultaneous access to water and 6% ethanol was determined between 0900 and 1500 h. In high-preferring males (normally covering > 60% of their daily fluid consumption in the form of ethanol), two injections with the corticosterone synthesis inhibitor metyrapone (50 mg/kg) at 0900 h and 1200 h for 4 consecutive days significantly reduced ethanol preference such that they preferred water over alcohol. Treatment with corticosterone (0.6 mg/kg) 2 h before each metyrapone injection partially cancelled this effect of the synthesis inhibitor. By contrast, there was no significant effect of metyrapone treatment on the drinking of ethanol in low-preferring rats (normally covering < 30% of their daily fluid consumption in the form of ethanol). These results suggest that the adrenal secretion of corticosterone directly or indirectly modulates the intake of alcohol in high-preferring rats.

Progesterone and bone: A closer link than previously realized

Article

Apr 2012
CLIMACTERIC

Decreasing rates of ovulation, hormonal changes, and increasing bone loss pre-date menopause by several years. Data suggest that, in addition to estradiol, progesterone may play a significant role in the interrelationship between the ovaries and the skeleton in women. Indeed, the differentiation of human osteoblasts from perimenopausal women has been shown to be dose-dependent on progesterone at physiological concentrations. Data from a pilot study in perimenopasual women also suggested that higher progesterone levels, as seen in the luteal phase of ovulatory cycles, may be associated with more bone formation and with slightly less bone resorption than anovulatory cycles in which progesterone levels are low (< 5.8 ng/ml). These data led to the initiation of a large, prospective, 2-year observational study in perimenopausal women (the PEKNO study). Interim data from the PEKNO study indicate that a decrease in ovulation correlated with an increase in the loss of bone mineral density (BMD). A meta-analysis estimated a BMD increase of 0.5% per year in women with normal ovulation, and a BMD decrease of 0.7% per year in young women with ovulatory disturbances (anovulation or short luteal phase). A meta-analysis in postmenopausal women demonstrated a 1.3% increase per year in BMD when receiving hormone replacement therapy with unopposed estrogens, and a further 0.4% increase in BMD in women receiving estrogens plus progestogens. The role of progesterone in bone metabolism in perimenopausal women who are estrogen-replete requires further study.

Testosterone levels in healthy men are related to amygdala reactivity and memory performance

Article

Feb 2012

Testosterone is a steroid hormone thought to influence both emotional and cognitive functions. It is unknown, however, if testosterone also affects the interaction between these two domains, such as the emotional arousal-induced enhancement of memory. Healthy subjects (N=234) encoded pictures taken from the International Affective Picture System (IAPS) during functional magnetic resonance imaging (fMRI) and underwent a free recall test 10 min after memory encoding. We show that higher endogenous testosterone levels at encoding were associated with higher arousal ratings of neutral pictures in men. fMRI analysis revealed that higher testosterone levels were related to increased brain activation in the amygdala during encoding of neutral pictures. Moreover, endogenous testosterone levels were positively correlated with the number of freely recalled neutral pictures. No such relations were found in women. These findings point to a male-specific role for testosterone in enhancing memory by increasing the biological salience of incoming information.

Regulation of Cancer Progression by -Endorphin Neuron

Article

Feb 2012
CANCER RES

Effects of Alcohol on the Endocrine System

Abstract

No full-text available