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Schematic illustration of relative finger lengths and possible association with typical physical features. Physical char- acteristics that develop in distinctly masculine and feminine ways are mostly caused by sex hormones . High prenatal testos- terone exposure leads to masculine 2D/4D digit ratio (lower than 1). Female undergo less androgenisation that results in 2D/4D digit ratio higher than 1. Finger lengths are associated with some cognitive abilities and also with risk for disease development.
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Testosterone is a steroid sex hormone with an important role in the physiology in both sexes. It is involved in the development of morphological and functional parameters of the body via multiple molecular mechanisms. Intensive research focused on testosterone reveals associations with cognitive abilities and behavior and its causative role in sex...
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... androgen exposure caused significantly lower 2D/4D when compared to healthy controls (Brown et al. 2002). Animal studies on bird eggs confirmed the prenatal androgen effect on 2D/4D (Romano et al. 2005). The 2D/4D digit ratio was found to be associated with many physiological, behavioral and cognitive parameters that are sexually dimorphic and influenced by hormonal activity, even the sexual orientation ( Fig. 6). Homosexuals of both sexes have a lower 2D/4D ratio when compared to heterosexuals suggesting higher androgen levels prenatally (van Goozen et al. 2002, Rahman and Wilson 2003). Finger ratio was measured in association with reproductive success in healthy men and women. For men, there is a negative association between low 2D/4D and higher number of children or sperm counts. Women display positive relationship between higher 2D/4D and fertility (Manning and Fink 2008). Very high feminine 2D/4D can be a risk factor for breast cancer (Belcher et al. 2009, Devine et al. 2010). On the other hand, atypically low digit ratio is believed to be associated with autism spectrum disor- ders (Bloom et al. 2010, Krajmer et al. 2011). It is sug- gested that prenatal testosterone levels promote devel- opment and maintenance of traits useful in male fight- ing sports related to aggressiveness. Digit ratio 2D/4D is negatively associated with sport success in men (Manning and Taylor 2001). Low 2D/4D is also related to higher sport abilities in females (Paul et al. 2006). In studies focused on digit ratio in relation to spatial orientation, many contradictions were found. Women exposed to higher prenatal androgen levels have lower 2D/4D (man-like) and perform better in spatial test and numerical tasks than women with a higher digit ratio (woman-like) (Kempel et al. 2005). In contrast, in males improvement in spatial ability occurred after a decrease in circulating testosterone levels. In the nor- mal range of testosterone levels, feminine 2D/4D in males is linked with best results in visual spatial tasks (Sanders et al. 2002). A recent study investigating implications for the relationship between prenatal tes- tosterone and academia shows social scientists of both sexes have a ratio consistent with the male norm (0.98) whilst scientists have a digit ratio consistent with the female norm (1.00). Both of these findings propose that the relationship between the 2D:4D ratio and visuo- spatial ability may reveal a U-shaped curve or other non-linear relationship (Brosnan 2006). They provoke also some speculations that 2D/4D can be related to spatial preferences rather than ability per se (Valla and Ceci 2011). Despite the 2D/4D is consider to be a rele- vant indicator of prenatal hormonal profile, recent studies brought inconsistent or controversial results that are difficult to interpret (Forstmeier et al. 2010, Medland et al. 2010, Valla and Ceci 2011). In some studies low 2D/4D on the right hand and high 2D/4D on the left hand are used as predictors of higher prena- tal androgen levels. Data from the right hand ...
Citations
... Some data reported conflicting results and supported a non-consistent effect of androgens (54). Studies on molecular mechanism of androgen action on the brain indicated that testosterone have a direct impact on glial cells thereby can modulate the myelinisation mechanism, synapse, and dendritic branching number as well as neuron growth (55). It has also been shown that even though gonadotropic neurons do not express androgen receptors, testosterone can modulate these neurons through a neuropeptide called kisspeptin which is not only expressed in the hypothalamic-pituitary-gonadal axis (HPG) but also in the limbic regions of the brain implicated in the emotional and cognitive behaviour (Mills et al., 2018. ...
Objective: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. Methods: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. Control group: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. Results: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. Conclusions: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.
... In men, testosterone plays a crucial role in the maintenance of muscular integrity, bone mineral density, and sexual function, with its deficiency potentially result in issues such as infertility, depression, fatigue, and decreased libido [3]. Despite being present at lower levels in women, testosterone exhibits greater sensitivity in females [4]. Emerging evidence suggests that testosterone levels may be correlated with suicidal behavior in females with bipolar disorder, and bioavailable testosterone is associated with the severity of COVID-19 infection in women [5,6]. ...
Objective
Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females.
Methods
Initially, a rigorous quality control process was employed to identify suitable instrumental single nucleotide polymorphisms (SNPs) associated with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined through a two-sample Mendelian randomization. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were applied in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Furthermore, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized to further validate the robustness of the results.
Results
Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1407, 95%CI: 1.0627–1.2244, P = 0.0015) and endometrial cancer (OR = 1.4610, 95%CI: 1.2695–1.6813, P = 1.22E-06). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1764, 95%CI: 1.0846–1.2761, P = 0.0005), cervical cancer(OR = 1.0020, 95%CI: 1.0007–1.0032, P = 0.0077), and endometrial cancer(OR = 1.4124, 95%CI: 1.2083–1.6511, P = 0.0001). Additionally, our results demonstrated a negative causal relationship between BT and ovarian cancer (OR = 0.8649, 95%CI: 0.7750–0.9653, P = 0.0320). However, no causal relationship was found between BT, TT and other types of cancer (corrected P > 0.05).
Conclusions
This study elucidates the role of testosterone on the development of breast cancer, endometrial cancer, ovarian cancer, and cervical cancer. It also hints at a potential but fragile link between testosterone and bladder cancer, as well as thyroid cancer. Nonetheless, it's worth noting that no statistically significant relationship between testosterone and various other types of cancer in females was identified.
... These hormones suppress atrophy and neurodegeneration induced by stress hormones in different brain parts [174][175][176] and induce neuronal plasticity and synaptic remodeling [177]. Moreover, testosterone improves mood and behavior and reforms cognitive skills [178]. Stress exposure downregulates testosterone and estradiol receptors in the hippocampus. ...
... Testosterone is converted to dihydrotestosterone (DHT) and estradiol, acting on androgen and estradiol receptors. Testosterone induces its effect via genomic and non-genomic pathways [178] and exerts anxiolytic and antidepressant effects by these receptors [180][181][182]. The hippocampus seems to be the main region that testosterone affects [179]. ...
Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.
... In men, testosterone plays a crucial role in the maintenance of muscular integrity, bone mineral density, and sexual function, and its de ciency may result in infertility, depression, fatigue, and decreased libido [3]. Despite circulating at lower levels in women, testosterone exhibits greater sensitivity in females [4]. Emerging evidence suggests that testosterone levels may correlate with suicidal behavior in females with bipolar disorder, and bioavailable testosterone is associated with the severity of COVID-19 infection in women [5,6]. ...
Objective: Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females.
Methods: Initially, a rigorous quality control process was used to identify suitable instrumental single nucleotide polymorphisms (SNPs) linked with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined via two-sample Mendelian randomization. A variety of analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Moreover, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized in order to further validate the robustness of the results.
Results: Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1184, 95%CI: 1.0448-1.1971, P = 0.0083) and endometrial cancer (OR = 1.4995, 95%CI: 1.3179-1.7061, P = 9.94E-09). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1403, 95%CI: 1.0574-1.2298, P = 0.0043), cervical cancer (OR = 1.0017, 95%CI: 1.0006-1.0028, P =0.0122), and endometrial cancer (OR = 1.5046, 95%CI: 1.3103-1.7277, P = 9.06E-08). However, no causal relationship was found with BT and TT on other types of cancer (corrected P> 0.05).
Conclusions: This study elucidates the role of testosterone in the development of breast cancer, endometrial cancer, and cervical cancer, while also indicating a potential tenuous link between testosterone and bladder cancer as well as skin cancer. Nonetheless, no statistically meaningful relationship between testosterone and various other types of cancer in females was observed.
... It is mainly synthesized by the Leydig cells of the testes in males, whereas the ovaries, the adrenal gland, and the placenta produce it in females. Biosynthesis of T also occurs in some regions of the brain (Durdiakova et al., 2011). This hormone is responsible for the development and maintenance of primary and secondary sexual characteristics in males such as the penis, muscles, and beard, through binding to intracellular receptors, modulation of ligandactivated ion channels, and interacting with neurotransmitters. ...
... A4 jest metabolitem pośrednim powstającym na drodze przekształcenia P4 w T [3]. Androgeny produkowane są przez komórki Leydiga jąder, jajniki i warstwę korową nadnerczy, regulując w sposób dymorficzny emocjonalne, motywacyjne oraz kognitywne aspekty zachowań seksualnych [5]. ...
Wraz ze wzrostem średniej długości życia i starzeniem się ludzkiej populacji, zwiększa się odsetek osób cierpiących na choroby neurodegeneracyjne (NDs). W przypadku choroby Alzheimera (AD), choroby Parkinsona (PD) i stwardnienia zanikowego bocznego (ALS), zaobserwowano wyraźną dysproporcję w zachorowalności w zależności od płci. Uważa się, że może to mieć związek z wpływem steroidów płciowych na ryzyko wystąpienia tych chorób. Dane epidemiologiczne pokazują, że na AD częściej cierpią kobiety, natomiast PD i ALS są bardziej rozpowszechnione u mężczyzn. Liczne badania wskazują na neuroprotekcyjne działanie estrogenów i potwierdzają, że czynniki redukujące ich poziom zwiększają ryzyko zachorowania na NDs. Odwrotne efekty zaobserwowano dla androgenów, chociaż dowiedziono także korzystnego wpływu tych hormonów. Zrozumienie potencjalnej roli steroidów płciowych i ich receptorów w patogenezie i przebiegu NDs może przyczynić się do lepszego poznania molekularnych mechanizmów leżących u podłoża tych schorzeń, a tym samym do opracowania skuteczniejszych sposobów prewencji i leczenia.
... The production of these hormones is regulated by the action of StAR, CYP17A1, and 3β-HSD (Figure 9). Calcium ions (Ca 2+ ) play a significant role in inducing the expression of these enzymes by bringing about the activation of transcription factors SF1, Sp1, Plox1, CREB, and NGF1β (KEGG: map04927) [58]. MMINA contributes by activating CatSper and StAR, CYP17A1, and 3βHSD gene expression. ...
Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were treated with saline, DMSO, CDDP, CDDP + MMINA, or MMINA. Reproductive hormones, antioxidant enzyme activity, histopathology, daily sperm production, and oxidative stress markers were examined. Western blot analysis was performed to access the expression of steroidogenic acute regulatory protein (StAR) and inflammatory biomarker expression in testis, while expression of calcium-dependent cation channel of sperm (CatSper) in epididymis was examined. The structural and dynamic molecular docking behavior of MMINA was analyzed using bioinformatics tools. The construction of molecular interactions was performed through KEGG, DAVID, and STRING databases. MMINA treatment reversed CDDP-induced nitric oxide (NO) and malondialdehyde (MDA) augmentation, while boosting the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the epididymis and testicular tissues. CDDP treatment significantly lowered sperm count, sperm motility, and epididymis sperm count. Furthermore, CDDP reduced epithelial height and tubular diameter and increased luminal diameter with impaired spermatogenesis. MMINA rescued testicular damage caused by CDDP. MMINA rescued CDDP-induced reproductive dysfunctions by upregulating the expression of the CatSper protein, which plays an essential role in sperm motility, MMINA increased testosterone secretion and StAR protein expression. MMINA downregulated the expression of NF-κB, STAT-3, COX-2, and TNF-α. Hydrogen bonding and hydrophobic interactions were predicted between MMINA and 3β-HSD, CatSper, NF-κβ, and TNFα. Molecular interactome outcomes depicted the formation of one hydrogen bond and one hydrophobic interaction between 3β-HSD that contributed to its strong binding with MMINA. CatSper also made one hydrophobic interaction and one hydrogen bond with MMINA but with a lower binding affinity of -7.7 relative to 3β-HSD, whereas MMINA made one hydrogen bond with NF-κβ residue Lys37 and TNF-α reside His91 and two hydrogen bonds with Lys244 and Thr456 of STAT3. Our experimental and in silico results revealed that MMINA boosted the antioxidant defense mechanism, restored the levels of fertility hormones, and suppressed histomorphological alterations.
... It is expected that the hormones, progesterone and testosterone might interact with nCoV. [12][13][14][15] Progesterone causes the endometrium transition from prolifera-tive phase to the secretory phase for maintain the blastocyst and maintain the pregnancy. It also plays an important role for maintaining the several types of tissues that are not belonged to the reproductive systems like mammary glands for breastfeeding, cardiovascular system bones. ...
SARS-CoV-2 is drastically spread across the globe in a short period of time and affects the lives of billions. There is a need to find the promising drugs like candidates against the inhibition of novel corona virus or SARS-CoV-2. Herein, the interaction on sex hormones (testosterone and progesterone) with Mpro of SARS-CoV-2 was investigated with the help of molecular docking. The binding energy for the formation complex between the progesterone and testosterone with main protease of SARS-CoV-2 are -86.05 and -91.84 kcal/mol, respectively. From this, it can be understood that testosterone showed better binding affinity with Mpro of nCoV and thus, more inhibition of the main protease. Then, the binding was further studied using molecular dynamics simulations at different temperatures (300, 310 and 325) K. It has been observed that the formations of complex between the Mpro of nCoV with testosterone/ progesterone is better at 300 K than 310 and 325 K. Further, it is found that the more effective binding of testosterone with Mpro of nCoV is observed than the progesterone based on the RMSD, RMSF and H-bond trajectories. Results indicate the promising nature of testosterone towards the inhibition of Mpro of nCoV.
... Testosterone regulates genomic expression through its metabolites, dihydrotestosterone (DHT), which binds to the androgen receptor, and estradiol, which binds to the estrogen receptor (Durdiakova et al., 2011). Little is known about the role of the androgen receptor in the mediation of PTSD symptomatology. ...
Post-traumatic stress disorder (PTSD) is a devastating illness with treatment that is effective in only approximately half of the population. This limited rate of response highlights the necessity for research into underlying individual biological mechanisms that mediate development and progression of this disease, allowing for identification of patient-specific treatments. PTSD has clear sex differences in both risk and symptom patterns. Thus, one approach is to characterize trauma-related changes between men and women who exhibit differences in treatment efficacy and response to trauma. Recent technological advances in sequencing have identified several genomic loci and transcriptional changes that are associated with post-trauma symptomatology. However, although the diagnosis of PTSD is more prevalent in women, the genetic factors underlying sex differences remain poorly understood. Here, we review recent work that highlights current understanding and limitations in the field of sex differences in PTSD and related symptomatology.
... Cholesterol via desmolase activity will produce pregnenolone, converted to 17-alpha-hydroxyprognelonone, to dehydroepiandrosterone, to 4-androstene-3,17-dione, and finally to testosterone. Alternative pathway to produce testosterone is via conversion of cholesterol to progesterone, to 17-alpha-hydroxyprogesterone, to 10 4-androstene-3,17-dione, to testosterone ( Figure 2). This hormone generally plays a role in the formation of masculine characteristics of the body. ...
Obesity can be defined as the excess of body fat. The prevalence of obesity worldwide increases in the last decades andcauses a higher risk of cardiovascular diseases. Male subjects tend to develop visceral (abdominal) obesity, which producespro-inflammatory adipokines. Obesity in males is associated with low testosterone levels. Several mechanisms have beenproposed to explain the link between male obesity and hypotestosterone, including increased aromatization oftestosterone to form estradiol, suppressing the Hypothalamus-Pituitary (HPT) axis due to pro-inflammatory adipokines, anddecrease of Sex Hormone Binding Globulin (SHBG) production. Because hypotestosterone in males with obesity is afunctional but reversible condition, it is essential to screen testosterone levels in obese males for early intervention andtreatment.
