Hormones (Athens, Greece)

Publications in this journal

• Article: Prevention of autoimmune hypothyroidism by modifying iodine intake and the use of tobacco and alcohol is manoeuvring between Scylla and Charybdis.

  Peter Laurberg, Stig Andersen, Inge Bülow Pedersen, Nils Knudsen, Allan Carlé
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  ABSTRACT: Although autoimmune hypothyroidism has generally been considered to be a disease that mainly develops because of genetic aberrations and for which adjustment of environment would bring about but slight risk modification, this understanding is increasingly appearing to be incorrect. We describe how iodine intake, smoking cessation and alcohol intake are all strong modifiers of risk that, combined, may influence risk by a factor of up to 30. Unfortunately, promotion of an environment leading to substantial lowering of the risk of autoimmune hypothyroidism (i.e. improvement of dietary iodine deficiency, decrease or cessation of smoking, and moderate alcohol intake) is not incorporated within current public health promoting programs. Nevertheless, it is increasingly becoming evident that knowledge of the importance of these factors for disease development is likely to assist in the planning of health promotion programs, while it will surely also be of value in the care of individual patients.
  Hormones (Athens, Greece) 01/2013; 12(1):30-8.
• Article: An overview of the pathogenesis of thyroid autoimmunity.

  Giulia Cogni, Luca Chiovato
  Hormones (Athens, Greece) 01/2013; 12(1):19-29.
• Article: Variations of urinary iodine during the first trimester of pregnancy in an iodine-replete area. Comparison with non-pregnant women.

  Atieh Amouzegar, Fereidoun Azizi
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  ABSTRACT: Objective: To assess variations of urinary iodine concentration (UIC) during a 4-week period among pregnant and non-pregnant women in an iodine-replete area. Design: Pregnant (in their first trimester of pregnancy) and non-pregnant women referred to two maternity hospitals in Tehran were consecutively recruited from September 2005 to March 2006. Urine samples (5-10 mL) were collected on an every-other-day basis for 4 weeks (i.e., 12 samples for each individual). UIC was determined using a modified Sandell-Kolthoff method. Results: Thirty-six pregnant and 32 non-pregnant women completed the study. Mean±SD age of pregnant women was 27.4±6.4 and of non-pregnant women 27.6±4.5 years (P=0.897). Mean±SD gestational age was 11±3.3 weeks in pregnant participants. Median UIC of <100, 100-149, 150-249, and ≥250 µg/L was present in 19.4, 25, 30.6, and 25% of pregnant, 15.6, 37.5, 34.4, and 12.5% of non-pregnant, and 17.6, 30.9, 32.4, and 19.1% of total individuals, respectively. Median UIC values of samples numbers 1 to 12 were not significantly different either in pregnant (P=0.591) or in non-pregnant subjects (P=0.745). Except for sample number 11, median UIC was not significantly different between pregnant versus non-pregnant women (P values >0.05). Mean SD values for UIC in samples numbers 1 to 12 in pregnant women was 138.4 (24.1-404) and in non-pregnant women 118 (29.5-272.4) µg/L (P=0.286). Conclusion: There was a wide intrapersonal variation in UIC values among pregnant and non-pregnant women residing in an iodine-replete area, supporting the notion that casual UIC would not reflect the iodine status of the individual.
  Hormones (Athens, Greece) 01/2013; 12(1):111-8.
• Article: Enhancing treatment of obesity by using a distracting mini-meal: a new approach to an old problem.

  Antonio Picarelli, Marco Di Tola, Fabio Tabacco, Mariacatia Marino, Raffaele Borghini, Tania D'Amico, Carla Lubrano, Patrizia Gargiulo
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  ABSTRACT: The management of obesity, apart from exercise, mainly involves a calorie restriction regimen. A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness, although several side-effects have previously been described. To improve patient compliance and diet effectiveness without incurring unpleasant side-effects, we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates. Two minutes before each of the three meals consumed daily, 32 obese patients were treated with a distracting mini-meal, 32 with metformin, and 32 with placebo. At baseline and after 1, 3, and 6 months of treatment, body weight, body mass index, waist circumference, fasting/post-prandial insulinaemia and glycaemia, homeostasis model assessment-index, triacylglycerols, and total cholesterol were evaluated. All patients showed good compliance. With the exception of post-prandial glycaemia, a significant reduction in all parameters was documented in every group, albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin. No one showed noteworthy side-effects. Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss. The beneficial effect of a distracting meal on insulin resistance, glucose, and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders.
  Hormones (Athens, Greece) 01/2013; 12(1):101-10.
• Article: Normocalcemic primary hyperparathyroidism: A newly emerging disease needing therapeutic intervention.

  Gonzalo Díaz-Soto, María Teresa Julián, Manel Puig-Domingo
  Hormones (Athens, Greece) 10/2012; 11(4):390-6.
• Article: Type 2 diabetes mellitus is associated with obesity, smoking and low socioeconomic status in large and representative samples of rural, urban, and suburban adult Greek populations.

  Nicholas Tentolouris, Alexandros Andrianakos, Georgios Karanikolas, Dimitrios Karamitsos, Panagiotis Trontzas, Petros Krachtis, Fotis Christoyannis, Elpiniki Tavaniotou, Zouboulio Nikolia, Evaggelia Kaskani, Leonidas Kontelis, Petros P Sfikakis
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  ABSTRACT: In this cross-sectional epidemiologic study we examined the association between type 2 diabetes mellitus and demographic, clinical, and socioeconomic parameters in large rural, urban and suburban populations of adult Greeks. Of the total target adult population (≥19 years, n=14233) in nine selected geographical regions covering rural, suburban, and urban areas of Greece, 10,647 subjects were included in the study. Data were collected by physicians who interviewed subjects at their homes between 1996 and 1999. A total of 8740 subjects participated (response rate 82.1%). Among participants there were 360 subjects with type 2 diabetes. Multivariate logistic regression analysis after adjustment for factors associated with type 2 DM in univariate analyses including occupation, education level, place of residence, and number of persons living together demonstrated that advancing age, obesity-but not overweight status-and smoking in the past were associated with higher odds of type 2 diabetes. Moreover, low socioeconomic status was associated with type 2 diabetes independently of the effects of age, obesity, and smoking. In large representative rural, urban, and suburban populations of adult Greeks, type 2 Diabetes was associated with advancing age, obesity, exposure to smoke, and low socioeconomic status.
  Hormones (Athens, Greece) 10/2012; 11(4):458-67.
• Article: Case Report: Primary pituitary non-Hodgkin's lymphoma developed following surgery and radiation of a pituitary macroadenoma.

  Labrini Papanastasiou, Theodora Pappa, Aikaterini Dasou, Efi Kyrodimou, George Kontogeorgos, Christianna Samara, Panagiotis Bacaracos, Athanasios Galanopoulos, George Piaditis
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  ABSTRACT: OBJECTIVE: Primary central nervous system (CNS) non-Hodgkin's lymphoma is a rarely encountered clinical entity. Here we present a case of a primary CNS diffuse large B-cell non-Hodgkin's lymphoma developed on a previously operated and irradiated pituitary macroadenoma. DESIGN-RESULTS: A 60-year-old woman presented with muscle weakness and eye lid ptosis. Thirty years ago, she was diagnosed with a non-functioning pituitary macroadenoma requiring repeated incomplete operations and conventional radiotherapy and accompanied by partial anterior pituitary deficiency. On admission, the magnetic resonance imaging (MRI) identified a pituitary sellar mass extending into the suprasellar region, compressing the optic chiasm and invading the left cavernous sinus. Following transsphenoidal surgery, the histological investigation revealed the presence of a diffuse large B-cell non-Hodgkin's lymphoma without other loci from the systemic staging. Following chemotherapy and despite a marked resolution of the neoplastic pituitary mass in the post-chemotherapy MRI scan, the patient's course was complicated with consciousness deterioration attributed to epileptic seizures and she died of a hospital acquired infection. CONCLUSIONS: Clinicians should include primary CNS lymphoma in the differential diagnosis of an isolated invasive sellar mass. The possible association of primary CNS lymphoma development with the history of operated and irradiated pituitary adenoma is herein discussed.
  Hormones (Athens, Greece) 10/2012; 11(4):488-94.
• Article: Primary aldosteronism associated with severe hypokalemic rhabdomyolysis.

  Wan-Ting Tsai, Yen Lin Chen, Wei Shiung Yang, Hong Da Lin, Chih Cheng Chien, Ching Ling Lin
  Hormones (Athens, Greece) 10/2012; 11(4):505-6.
• Article: Differences in plasma apelin and visfatin levels between patients with type 1 diabetes mellitus and healthy subjects and response after acute hyperglycemia and insulin administration.

  Kleopatra Alexiadou, Alexander Kokkinos, Stavros Liatis, Despoina Perrea, Nicholas Katsilambros, Nicholas Tentolouris
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  ABSTRACT: OBJECTIVE. Previous data suggest that apelin and visfatin play a role in metabolism and glucose homeostasis. The aim of the present study was to determine differences in plasma apelin and visfatin concentrations between healthy subjects and patients with type 1 diabetes mellitus and to study the effect of hyperglycemia and insulin administration on their levels in patients with type 1 diabetes mellitus. DESIGN. One hundred patients with T1DM and 52 healthy subjects were examined. Nine patients with type 1 diabetes and 9 controls participated in a further study. In the main study, blood samples were taken after a 12-hour fast. In a further study, an oral glucose tolerance test was performed on two occasions. In session A, at baseline, insulin lispro (7 units) was administered subcutaneously to the type 1 diabetic patients, while a placebo injection was administered to controls. In session B, no insulin or placebo was administered. Apelin, visfatin, insulin and glucose levels were measured at baseline and 10, 20, 30, 60, 90, 120, 150 and 180 min after glucose consumption. RESULTS AND CONCLUSIONS. Fasting plasma apelin concentrations were higher (p<0.001), while fasting visfatin levels tended to be lower (p=0.06) in patients with type 1 diabetes in comparison to healthy subjects. In the diabetes group, fasting apelin (but not visfatin) correlated with HDL-C (p=0.001). Apelin and visfatin did not change significantly during the oral glucose tolerance test in either group with or without exogenous insulin administration.
  Hormones (Athens, Greece) 10/2012; 11(4):444-50.
• Article: The predictive role of 24h RAIU with respect to the outcome of low fixed dose radioiodine therapy in patients with diffuse toxic goite.

  Nishikant Damle, Chandrasekhar Bal, Praveen Kumar, Ramamohan Reddy, Deepali Virkar
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  ABSTRACT: Radioactive iodine uptake (RAIU) is a test used to differentiate hyperthyroidism from thyroiditis and to calculate the radioiodine dose for treatment of Graves' disease. We aimed to evaluate the predictive role of 24h RAIU with respect to the outcome of radioiodine therapy in patients with diffuse toxic goiter (DTG). Case records of patients with DTG treated with radioactive iodine were reviewed retrospectively. Patients were divided into two groups based on 24h RAIU (normal range: 15% - 35% at 24 h): the first group included patients with 24h RAIU values equal to or less than 50%, while the second group included patients with 24h RAIU values of over 50%. Gland size, duration of disease, treatment with antithyroid drugs (ATD) and its duration were the other factors considered. Success of the first dose of 131I was defined as a euthyroid or hypothyroid status at 12 months post-therapy without the need for additional radioiodine or ATD therapy. Data were analyzed with 95% power and 1% type I error (α=0.01). Six hundred thirty-three (633) consecutive patients with DTG were given a fixed-dose (5mCi) of radioiodine between January 1987 and December 2006. One hundred seventy-five patients (175) had an RAIU ≤50% and 458 patients had an RAIU >50%. First-dose success rate in the former group was 81.7% and in the second group 68.6% (p=0.001). The overall first-dose success was 72%. Multivariate analysis confirmed the significant role of 24h RAIU data to predict a successful outcome. A 24h RAIU value of ≤50% appears to be associated with a significantly better outcome compared to that of a 24h RAIU value of >50% in patients with DTG given as treatment a fixed dose of 185 MBq radioiodine.
  Hormones (Athens, Greece) 10/2012; 11(4):451-7.
• Article: What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

  Jana Phillips, Honey E East, Sarah E French, Eugen Melcescu, Robert D Hamilton, William C Nicholas, Jonathan F Fratkin, Andrew D Parent, Gustavo Luzardo, Christian A Koch
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  ABSTRACT: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.
  Hormones (Athens, Greece) 10/2012; 11(4):477-82.
• Article: Is the 250 μg ACTH test a useful tool for the diagnosis of central hypoadrenalism in adult patients with pituitary disorders?

  Emanuele Ferrante, Valentina Morelli, Claudia Giavoli, Giovanna Mantovani, Elisa Verrua, Elisa Sala, Elena Malcmiodi, Silvia Bergamaschi, Eriselda Profka, Elisa Cairoli, Serena Palmieri, Iacopo Chiodini, Andrea Gerardo Lania, Anna Spada, Paolo Beck Peccoz
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  ABSTRACT: The diagnosis of hypothalamic-pituitary-adrenal insufficiency (HPAI) is a major clinical challenge. The gold standard procedure remains insulin tolerance test (ITT). This study aimed to evaluate the usefulness of standard-dose corticotrophin stimulation test (SDCT) in diagnosing HPAI. In this prospective study we performed SDCT and ITT in 55 consecutive patients (37F/18M) affected by pituitary disorders. A normal response to ITT was found in 44 patients, while HPAI was diagnosed in 11. Using ITT as reference test, the ROC curve showed that a cortisol value of 18 µg/dl (500 nmol/L) at 30 min or 21.8 µg/dl (600 nmol/L) at 60 min after SDCT represents the best compromise between sensitivity and specificity in diagnosing HPAI. Moreover, 30 min cortisol values >20.3 µg/dl (560 nmol/L) or 60 min cortisol values >24.1 µg/dl (665 nmol/L) exclude HPAI. Four out of 15 patients of Group A, previously non-respondent to SDCT, showed a normal response to a second SDCT. SDCT is not a reliable tool to identify HPAI, but it appears to be more useful in confirming the normality of HPA function. When SDCT fails to exclude HPAI, ITT should be performed. If ITT is contraindicated, retesting patients by SDCT is useful before starting an unnecessary replacement therapy.
  Hormones (Athens, Greece) 10/2012; 11(4):428-35.
• Article: 45,X/46,XY mosaicism: a cause of short stature in males.

  Alexandra Efthymiadou, Eunice G Stefanou, Dionisios Chrysis
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  ABSTRACT: 45,X/46,XY mosaicism is associated with a broad spectrum of phenotypes ranging from apparently normal male development to individuals with incomplete sexual differentiation and clinical signs of Turner syndrome in both males and females. The most common presentation among individuals with a 45,X/46,XY karyotype is sexual ambiguity, accounting for approximately 60% of cases, while the least common category of 45,X/46,XY patients consists of those with bilaterally descended testes, found in 11-12%. We report on two patients with an apparently normal male phenotype and 45,X/46,XY mosaicism who were diagnosed postnatally because of short stature. Both of these boys presented at the age of 15 years with short stature, minor Turner-like stigmata, normal male external genitalia and spontaneous pubertal development. One of them had coarctaction of the aorta with bicuspid aortic valve, an uncommon clinical feature in boys with mosaicism. The same patient underwent a trial of GH replacement therapy with poor response and his sperm analysis revealed azoospermia. Like our patients, most mosaic 45,X/46,XY children with bilateral scrotal testes go unrecognised at birth and throughout childhood unless they have somatic features of Turner syndrome or significant growth retardation. We recommend that boys with otherwise unexplained short stature, being short for their families, should be karyotyped routinely as is recommended in short-stature girls. In addition, boys with 45,X/46,XY mosaicism require a thorough clinical evaluation similar to that performed in girls with Turner syndrome and must be routinely followed up for their potential to respond favorably to GH treatment and for late onset abnormalities, such as infertility and gonadal tumors.
  Hormones (Athens, Greece) 10/2012; 11(4):501-4.
• Article: Increased primary autoimmune thyroid diseases and thyroid antibodies in sarcoidosis: evidence for an under-recognised extrathoracic involvement in sarcoidosis?

  Foteini Malli, Alexandra Bargiota, Kathrin Theodoridou, Zoi Florou, Fotini Bardaka, George N Koukoulis, Konstantinos I Gourgoulianis, Zoe Daniil
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  ABSTRACT: Sarcoidosis has been associated with thyroid diseases. However, until today no definite conclusions have been drawn. We aimed to assess the frequency of thyroid disorders and the levels of thyroid hormones and thyroid antibodies in 68 sarcoidosis patients and 75 controls. Additionally, we performed ultrasonography and fine-needle aspiration. In this prospective case control study conducted in the University Hospital of Larissa, Greece, overt thyroid disease was present in 29.4% of patients and 16.1% of patients presented clinical autoimmune thyroid disease. Sarcoidosis patients had a significantly higher frequency of serological autoimmunity. Female patients had significantly increased frequency of positive TSH receptor antibodies (TRAbs) and antithyroid peroxidase antibodies (TPOAbs) when compared to gender-matched controls (40% vs 0%, p<0.001, and 28.8% vs 11.86%, p=0.029, respectively). The hypoechoic pattern of the thyroid was more frequent in female patients vs controls (p<0.001). Male patients had a higher frequency of TRAbs and hypoechoic pattern of the thyroid gland (43.4% vs 0%, p=0.002, and 39.1% vs 6.25%, p=0.021, respectively). Indices of thyroid autoimmune disease were significantly more frequent in sarcoidosis patients vs gender-matched controls. Increased TPOAbs were significantly associated with clinical autoimmune disease in sarcoidosis. Overall, the findings derived from this study suggest that thyroid disorders are frequent in sarcoidosis. This association may potentially be the result of increased thyroid antibodies.
  Hormones (Athens, Greece) 10/2012; 11(4):436-43.
• Article: Prediction of maternal and neonatal adverse outcomes in pregnant women treated for hypothyroidism.

  Maria K Poulasouchidou, Dimitrios G Goulis, Pavlos Poulakos, Gesthimani Mintziori, Apostolos Athanasiadis, Grigorios Grimbizis, Basil C Tarlatzis
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  ABSTRACT: To examine whether the concentrations of maternal serum TSH and free thyroxine (fT4) through pregnancy, the presence of thyroid autoimmunity (TAI) or the dose of levo-thyroxine (LT4) replacement can predict the occurrence of maternal or fetal/neonatal complications in pregnant women treated for maternal hypothyroidism. The study included 92 women with singleton pregnancies and primary hypothyroidism on LT4 replacement. Maternal serum TSH, fT4, thyroid auto-antibodies and doses of LT4 were monitored throughout pregnancy. All maternal and fetal/neonatal complications were recorded. The overall prevalence of maternal and neonatal complications was 24.1%. Neither maternal TSH/fT4 concentrations, presence of TAI nor dose of LT4 could predict the occurrence of complications. Pre-pregnancy body mass index (BMI) was higher in women who developed maternal complications [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5, p=0.007) and gestational week at delivery was lower in pregnancies complicated by neonatal (OR 0.5, 95% CI 0.3-0.8, p=0.001) or any type of complications (OR 0.6, 95% CI 0.4-0.9, p=0.008). The occurrence of maternal or fetal/neonatal complications in pregnant women treated for hypothyroidism cannot be predicted by maternal TSH/fT4 through pregnancy, presence of TAI or dose of LT4 replacement.
  Hormones (Athens, Greece) 10/2012; 11(4):468-76.
• Article: Anatomical localization of insulinomas: still a need to combine a set of diagnostic procedures.

  Gianluca Tamagno, Donal O'Shea
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  ABSTRACT: The diagnosis of insulinoma is based on universally defined clinical and laboratory parameters (Whipple triad and fasting test). Pre-operative tumor localization is the main challenge in the diagnostic management of insulinomas. The pre-operative and/or intra-operative localization of the tumor is required for the optimal surgical approach. We describe two cases of insulinoma characterized by a typical clinical presentation, a positive diagnosis on fasting test, and computerized tomography failure in localizing the tumor. In the first patient, angiography with hepatic venous sampling after calcium stimulation correctly localized pre-operatively the region of the pancreas where the tumor was and, following intra-operative investigations, the lesion was successfully enucleated. In the second patient, angiography with hepatic venous sampling after calcium stimulation failed to identify the region of the insulinoma, which was detected by intra-operative ultrasound and successfully enucleated. Invasive pre-operative procedures for tumor regionalization and/or localization (angiography with hepatic venous sampling after calcium stimulation, endoscopic ultrasound) should be performed in cases where the tumor cannot be localized with enough certainty by non-invasive imaging. However, a careful intra-operative study should be performed in all patients undergoing surgery to complete the information obtained pre-operatively and to exclude the presence of other smaller lesions.
  Hormones (Athens, Greece) 10/2012; 11(4):483-7.
• Article: Endocrine, paracrine, and autocrine placental mediators in labor.

  Zoe Iliodromiti, Nikolaos Antonakopoulos, Stavros Sifakis, Panagiotis Tsikouras, Angelos Daniilidis, Kostantinos Dafopoulos, Dimitrios Botsis, Nikolaos Vrachnis
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  ABSTRACT: Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.
  Hormones (Athens, Greece) 10/2012; 11(4):397-409.