Impacts of Androgen Abuse and Overtraining on Endocrine Profile in Bodybuilders

Abuse of androgens and overtraining expose bodybuilders to multifactorial stress influences related to endocrine activity. Endocrine responses in 23 bodybuilder athletes were investigated after a strength training period, during which they were taking high doses of androgenic-anabolic steroids. Serum concentrations of TSH, T3, and T4 were unchanged significantly. Serum LH and FSH concentrations decreased dramatically (P<0.05). In addition, low mean concentration of serum testosterone was recorded, with more substantial reduction in participants of elder ages. The multiple regression model used in this analysis supported this inference. On the other hand, a positive association was observed between levels of blood lipids (total cholesterol, triglyceride) and the outcome predictor (mean serum testosterone level). The results also suggested a negative correlation between testosterone level and each of age and HDL level. The current study shows that excessive bodybuilding exercise has an impact on the hypothalamic–pituitary–thyroid (HPT) axis in top-level athletes. Also, simultaneous usage of anabolic steroids induces extreme shifts in the hypothalamic-pituitary–gonadal (HPGA) axis, which is reflected as changes in testosterone level, development of the overtraining syndrome, and adverse influences on hormonal control.

The relation between obesity, kisspeptin, leptin, and male fertility

Over the past decades, obesity and infertility in men increased in parallel, and the association between both phenomena have been examined by several researchers. despite the fact that there is no agreement, obesity appears to affect the reproductive potential of men through various mechanisms, such as changes in the hypothalamic-pituitary-testicular (HPT) axis, spermatogenesis, sperm quality and/or alteration of sexual health. Leptin is a hormone produced by the adipose tissue, and its production elevates with increasing body fat. Many studies have supported the relationship between raised leptin production and reproductive function regulation. In fact, Leptin acts on the HPT axis in men at all levels. However, most obese men are insensitive to increased production of endogenous leptin and functional leptin resistance development. Recently, it has been recommended that Kisspeptin neurons mediate the leptin’s effects on the reproductive system. Kisspeptin binding to its receptor on gonadotropin-releasing hormone (GnRH) neurons, activates the mammal’s reproductive axis and stimulates GnRH release. Increasing infertility associated with obesity is probably mediated by the Kisspeptin-GnRH pathway. In this review, the link between obesity, kisspeptin, leptin, and male fertility will be discussed.

Thyroid Disease Among Workers Exposed To Perfluorooctanoic Acid (PFOA)

Background: Perfluorooctanoic Acid (PFOA) is one of the Perfluoroalkyl acids family that can affect human health. It can act as an endocrine disruptors which interfered the hypothalamus–pituitary–thyroid (HPT) axis and targeted the biosynthesis and secretion of thyroid hormones, which can caused thyroid diseases. To determine the causal relationship between PFOA and thyroid diseases, it is necessary to look for some evidence regarding this relationship. The search for evidence is also complemented by a seven-step occupational disease assessment to establish occupational diseases.Methods: The literature searching using the electronic database “PubMed”, “Cochrane”, and “Scopus” search engine. The keyword is “PFOA” “perfluoroalkyl substances” “perfluorooctanoic acid” “perfluorooctanoate” AND “thyroid disease” “thyroid function” “thyroid parameters” combined with MeSH and Title/Abstract terms. The inclusion criteria are research on humans, English language, free full article and the exclusion is duplicate articles.Result: From the five literature obtained, there are differences in results. Four articles stated that there are association between PFOA and thyroid diseases but one articles stated PFOA concentrations measured in this study were not associated with thyroid hormones.Conclusion: Althought most articles stated there are associations between PFOA and thyroid disease but it does not mean that PFOA can caused thyroid disease so it is still not clear the causal relationship between PFOA and thyroid disease especially in occupational setting.

Suppression of the hypothalamic-pituitary-thyroid axis is associated with the severity of prognosis in hospitalized patients with COVID-19

Background The outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19). Methods In this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status. Results Among 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07–105.7), 23.1 (95% CI 5.75–92.8), and 4.04 (95% CI 0.69–23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56–5.05), 4.68 (95% CI 1.76–12.4), and 2.63 (95% CI 1.09–6.36) respectively. Conclusions Our study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.

Hyperoxia Leads to Transient Endocrine Alterations in the Neonatal Rat During Postnatal Development

Introduction: High oxygen concentrations have been identified as one factor contributing to the pathogenesis of the retinopathia of prematurity, chronic lung disease of the preterm infant and preterm brain injury. Preterm infants also show short- and long-term alterations of the endocrine system. If hyperoxia is one pathogenetic factor has not been investigated yet. With regard to the high prevalence of neurodevelopmental impairments in preterm infants, the hypothalamus-pituitary-thyroid (HPT) axis, the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-somatotropic (HPS) axis are of special interest due to their important role in neurodevelopment.Objective: The aim of this study was to investigate the effect of hyperoxia on the endocrine system in the neonatal rat by analyzing the activities of the HPT, HPA and HPS axes, respectively.Methods: Three-days old Wistar rats were exposed to hyperoxia (oxygen 80%, 48 h). On postnatal day 5 (P5) and P11, transcript levels of thyroid-stimulating hormone (TSH), proopiomelanocortin and growth hormone (GH) were analyzed in pituitary sections by in situ hybridization. Serologic quantification of TSH and thyroxine (T4), adrenocorticotropic hormone and GH were performed by Multiplex analysis and Enzyme-linked Immunosorbent Assay.Results: At P5, significantly lower GH levels were observed in pituitaries (mRNA) and in sera of rats exposed to hyperoxia. Serum TSH was significantly elevated without changes in T4.Conclusion: This is the first study demonstrating transient endocrine alterations following hyperoxia in the neonatal rat making oxygen a possible contributor to the pathogenesis of endocrine alterations seen in preterm infants. Considering the detrimental multi-organ effects of hyperoxia on the immature organism, a rational use of therapeutic oxygen in the treatrnent of preterm infants is of utmost importance.

The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis

Background. Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. Methods. We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. Results. Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04 ) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04 ). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. Conclusion. Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.

Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic–pituitary–thyroid axis

Fasting induces profound changes in the hypothalamic–pituitary–thyroid (HPT) axis. After binding thyroid hormone (TH), the TH receptor beta 2 isoform (THRB2) represses Trh and Tsh subunit genes and is the principle negative regulator of the HPT axis. Using mass spectrometry, we identified a major phosphorylation site in the AF-1 domain of THRB2 (serine 101, S101), which is conserved among many members of the nuclear hormone receptor superfamily. More than 50% of THRB2 is phosphorylated at S101 in cultured thyrotrophs (TαT1.1) and in the mouse pituitary. All other THR isoforms lack this site and exhibit limited overall levels of phosphorylation. To determine the importance of THRB2 S101 phosphorylation, we used the TαT1.1 cell line and S101A mutant knock-in mice (Thrb2S101A). We found that TH promoted S101 THRB2 phosphorylation and was essential for repression of the axis at physiologic TH concentrations. In mice, THRB2 phosphorylation was also increased by fasting and mimicked Trh and Tshb repression by TH. In vitro studies demonstrated that a master metabolic sensor, AMP-activated kinase (AMPK) induced phosphorylation at the same site and caused Tshb repression independent of TH. Furthermore, we identified cyclin-dependent kinase 2 (CDK2) as a direct kinase phosphorylating THRB2 S101 and propose that AMPK or TH increase S101 phosphorylation through the activity of CDK2. This study provides a physiologically relevant function for THR phosphorylation, which permits nutritional deprivation and TH to use a common mechanism for acute suppression of the HPT axis.

Impairment of the Hypothalamus–Pituitary–Thyroid Axis Caused by Naturally Occurring GATA2 Mutations In Vitro

The transcription factor GATA2 regulates gene expression in several cells and tissues, including hematopoietic tissues and the central nervous system. Recent studies revealed that loss-of-function mutations in GATA2 are associated with hematological disorders. Our earlier in vitro studies showed that GATA2 plays an essential role in the hypothalamus–pituitary–thyroid axis (HPT axis) by regulating the genes encoding prepro-thyrotropin-releasing hormone (preproTRH) and thyroid-stimulating hormone β (TSHβ). However, the effect of GATA2 mutants on the transcriptional activity of their promoters remains unelucidated. In this study, we created five human GATA2 mutations (R308P, T354M, R396Q, R398W, and S447R) that were reported to be associated with hematological disorders and analyzed their functional properties, including transactivation potential and DNA-binding capacity toward the preproTRH and the TSHβ promoters. Three mutations (T354M, R396Q, and R398W) within the C-terminal zinc-finger domain reduced the basal GATA2 transcriptional activity on both the preproTRH and the TSHβ promoters with a significant loss of DNA binding affinity. Interestingly, only the R398W mutation reduced the GATA2 protein expression. Subsequent analysis demonstrated that the R398W mutation possibly facilitated the GATA2 degradation process. R308P and S447R mutants exhibited decreased transcriptional activity under protein kinase C compared to the wild-type protein. In conclusion, we demonstrated that naturally occurring GATA2 mutations impair the HPT axis through differential functional mechanisms in vitro.

Comparative Efficacy of Haizao Yuhu Decoction Composed of Different Varieties of Glycyrrhiza in Goiter Rats

In traditional Chinese medicine, Glycyrrhiza and Sargassum are one pair of the “18 incompatible medicaments,” which in theory cannot be used together. However, since ancient times, many reports have described using compounds containing both Glycyrrhiza and Sargassum to treat diseases. Haizao Yuhu Decoction (HYD), which contains both ingredients, is mainly used to treat goiter. Chinese Pharmacopoeia officially recorded three varieties of Glycyrrhiza: Glycyrrhiza uralensis, Glycyrrhiza inflata, and Glycyrrhiza glabra. These three varieties have certain differences in chemical composition and pharmacological effects. The purpose of the present study was to investigate whether the HYD containing different varieties of Glycyrrhiza and Sargassum had different therapeutic effects in rats with goiter and to elucidate the underlying mechanism of any difference. In this study, propylthiouracil (PTU) was used to replicate the goiter model, then HYDs containing different varieties of Glycyrrhiza were used for treatment for four weeks, and then the relevant indicators were tested. The results demonstrated that HYD had antigoiter effects, alleviated the pathological changes in the thyroid tissue, and restored the abnormal serum levels of hormones related to thyroid function induced by PTU. HYD containing Glycyrrhiza uralensis had the best therapeutic effect in rats with PTU-induced goiter. The antigoiter effect of HYD may function through the hypothalamic-pituitary-thyroid (HPT) axis, inhibit the expression of the Tg and NIS genes, and regulate the synthesis of thyroid hormones, thereby reducing the excessive stimulation of TSH in thyroid cells. In addition, HYD also prevented goiter by promoting thyroid cell apoptosis and inhibiting the ERK/RSK1 pathway of cell proliferation. In conclusion, three types of HYD had different therapeutic effects in rats with goiter, which might be caused by the compatibility of different varieties of Glycyrrhiza and Sargassum.