Hormone Axis Research Articles

Developmental exposure to thyroid disruptors: misprogramming of the brain's stem cells in later life?

Developmental exposure to thyroid disruptors: misprogramming of the brain's stem cells in later life?

Effects of Perinatally Acquired Cytomegalovirus Infection on Growth Hormone Axis

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well.

ROLE OF YOGIC PRACTICES IN POSTPARTUM CARE

Introduction: Child birth is a critical event in a woman's life. It comes with responsibility, physical-emotional stress and strain along with anatomical, physiological and hormonal changes. Maternal physical and emotional health issues are quite common after parturition. Yoga can be an important management tool in these conditions. Yoga is a cost-effective therapy and can be administered easily with only initial guidance. The mother can perform it at home after properly learning from trained personnel. Materials and Methods: This is a conceptual study based on elaboration of references from various books on Yoga, research articles and web sources. Discussion: Yogic practices with their holistic and psycho-physiological approach help in management of various physical conditions as well as emotional and psychological issues. Overall effects of all these practices are reduction in pain, improved mood status and sleep, reduced stress, anxiety and depression, improved physiological functions and re-established hormonal axis. The specic practices performed for specic health conditions help in their management. Conclusion: Yogic practices help in speedy recovery of the body for normal functioning of daily life in the postpartum women. They help in management of various postpartum health conditions and in coping with stress and give a positive sense of wellbeing.

New Insights into the Role of the Insulin-Like Growth Factors in Breast Cancer

The insulin-like growth factor-1 hormonal axis has emerged in recent years as a promising therapeutic target in oncology. Empirical support to this view was provided by pre-clinical studies showing that insulin-like growth factor-1 receptor expression and activation constitute fundamental prerequisites for breast cancer development. Unfortunately, the vast majority of phase III clinical trials using monoclonal antibodies against the receptor have been disappointing. As a result of these negative outcomes there is an urgent need to identify predictive biomarkers that may identify potential responders. The present review article is aimed at providing an overview of the role of the insulin-like growth factor-1 axis in breast cancer. Circulating insulin-like growth factor-1 constitutes a risk factor for a number of malignancies, including breast cancer, and various members of the insulin-like growth factor-1 system are produced by the tumoral cells or by stromal cells. In addition, we provide evidence that the mechanism of action of insulin-like growth factor-1 involves interactions with the estrogen receptor as well as with the breast cancer gene-1. Finally, lifestyle factors that are related to insulin-like growth factor-1, such as obesity, have been suggested to have an effect on breast cancer.

Growth hormone’s impact on adipose tissue and aging

A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the healthspan and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormone.

Níveis dos hormônios do eixo hipotálamo-pituitária-adrenal no líquido cefalorraquidiano de pacientes com CCL e demência devido à doença de Alzheimer: uma revisão sistemática

ABSTRACT Underlying the neuropsychological manifestations of Alzheimer’s disease (AD), hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subsequent hypercortisolemia have been proposed as major mechanisms driving AD progression from mild cognitive impairment (MCI) to the onset of dementia. Nonetheless, changes in cerebrospinal fluid (CSF) levels of HPA axis hormones remain controversial despite their potential in AD diagnosis and prognosis testing. Objective: This study aimed to review the evidence of the variation in CSF levels of CRH, ACTH, and cortisol in subjects with mild cognitive impairment (MCI) and AD compared with subjects without cognitive disorders. Methods: A systematic review was conducted in MEDLINE, EMBASE, and Web of Science databases on July 5, 2022. Results: Seventeen observational studies were included. The results from the compiled investigations showed that individuals with AD exhibit a significant elevation of CSF cortisol levels which appear to correlate with the presence of the ApoE-ε4 allele, being higher in those homozygous for this allele. The variation of CSF CRH and ACTH levels in AD, on the other hand, is still inconclusive. Moreover, most studies found no significant difference in CSF cortisol levels in individuals with MCI compared to healthy subjects and patients with AD. Conclusion: The findings gathered in this review disclose a significant elevation of CSF cortisol levels in AD. Future investigations are warranted to elucidate the potential use of CSF cortisol as a biomarker in AD-associated dementia.

Exploring the regulatory mechanism of osteoporosis based on intestinal flora: A review.

Osteoporosis is 1 of the common diseases of bone metabolism in clinic. With the aging of the population in China, osteoporosis is becoming more and more serious, and it has become 1 of the major public health problems. However, traditional therapies, such as calcium therapy and estrogen therapy, can cause serious adverse effects and damage to the body when ingested over a long period of time. Therefore, there is an urgent need to explore alternative therapies with less side effects in clinical practice. Intestinal flora is a hot topic of research in recent years. It has been studied in inflammatory bowel disease, diabetes, depression and so on. Recently, intestinal flora has received increasing attention in the pathways regulating bone metabolism. This paper contains a review of recent studies related to osteoporosis and gut flora in terms of its metabolites, immune, endocrine, and brain-gut axis pathways. The strong association between intestinal flora and bone metabolism suggests, to some extent, that intestinal flora can be a potential target for osteoporosis prevention and treatment, providing new ideas and therapies for the prevention and treatment of osteoporosis.

Evaluation of Neuroendocrine Dysfunction Following Acute Aneurysmal Subarachnoid Hemorrhage

Background and Aim: In the management of aneurysmal subarachnoid hemorrhage (aSAH), endocrine dysfunction is infrequently considered. Pituitary (neuroendocrine) dysfunction is highly prevalent after aSAH, leading to residual symptoms such as decreased cognition and quality of life. Although hypopituitarism following SAH may present with non-specific subtle symptoms, it can lead to potentially serious consequences if left undiagnosed. Methods and Materials/Patients: This study was performed to observe the incidence and pattern of neuroendocrine alterations in cases of acute aSAH. A total of 25 patients with acute SAH within 7 days of ictus were included in this prospective study, and an endocrine assessment was performed. The pituitary axes were evaluated for possible dysfunctions, including somatotropic, gonadotropic, corticotropic, and thyrotropic axes. Results: A total of 25 SAH cases (10 males and 15 females; mean age 55.24 years) were included in the study. Aneurysms were more commonly found in the anterior circulation (n=22) than in the posterior circulation (n=3). Most of the patients presented with the Hunt-Hess grade of 1, followed by grades 3, 2, and 4, respectively. Growth hormone deficiency (48%) was the most common pituitary dysfunction, followed by adrenocorticotrophic hormone (24%), gonadotropins (FSH/LH) (24%), and thyroid stimulating hormone (16%) deficiencies, respectively. Single pituitary axis neuroendocrine dysfunction was noted in 9 patients (36%) and multiple pituitary axes dysfunction was observed in 8 patients (32%). Overall, 17 patients (68%) had neuroendocrine dysfunction in single or multiple pituitary hormone axes. Conclusion: Neuroendocrine dysfunction in acute aSAH is 68%. Accordingly, 32% of the participants had single-axis pituitary dysfunction and 36% had multiple axes pituitary dysfunction. The most common endocrine dysfunction is growth hormone deficiency (48%), followed by adrenocorticotrophic hormone, gonadotropins (LH & FSH), and thyroid stimulating hormone. Therefore, it is suggested to include hormonal evaluation in the management of acute SAH for better clinical outcomes.

The progression of secondary diabetes: A review of modeling studies.

Mathematical modeling has provided quantitative information consistent with experimental data, greatly improving our understanding of the progression of type 1 and type 2 diabetes. However, diabetes is a complex metabolic disease and has been found to be involved in crosstalk interactions with diverse endocrine diseases. Mathematical models have also been developed to investigate the quantitative impact of various hormonal disorders on glucose imbalance, advancing the precision treatment for secondary diabetes. Here we review the models established for the study of dysglycemia induced by hormonal disorders, such as excessive glucocorticoids, epinephrine, and growth hormone. To investigate the influence of hyperthyroidism on the glucose regulatory system, we also propose a hyperthyroid-diabetes progression model. Model simulations indicate that timely thyroid treatment can halt the progression of hyperglycemia and prevent beta-cell failure. This highlights the diagnosis of hormonal disorders, together withblood sugar tests, as significant measures for the early diagnosis and treatment of diabetes. The work recapitulates updated biological research on the interactions between the glucose regulatory system and other endocrine axes. Further mathematical modeling of secondary diabetes is desired to promote the quantitative study of the disease and the development of individualized diabetic therapies.

Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review.

Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of ED on humans, mammals, and aquatic organisms, this work aimed to review the state-of-the-art regarding the toxic effects of MCs and CYN at this level. It has been evidenced that MCs have been more extensively investigated than CYN. Reported results are contradictory, with the presence or absence of effects, but experimental conditions also vary to a great extent. In general, both toxins have shown ED activity mediated by very different mechanisms, such as estrogenic responses via a binding estrogen receptor (ER), pathological changes in several organs and cells (testis, ovarian cells), and a decreased gonad-somatic index. Moreover, toxic effects mediated by reactive oxygen species (ROS), changes in transcriptional responses on several endocrine axes and steroidogenesis-related genes, and changes in hormone levels have also been reported. Further research is required in a risk assessment frame because official protocols for assessment of endocrine disrupters have not been used. Moreover, the use of advanced techniques would aid in deciphering cyanotoxins dose-response relationships in relation to their ED potential.

Endocrine-disrupting chemicals (EDCs) and cancer: new perspectives on an old relationship.

Environmental endocrine-disrupting chemicals (EDCs) are a mixture of chemical compounds capable to interfere with endocrine axis at different levels and to which population is daily exposed. This paper aims to review the relationship between EDCs and breast, prostate, testicle, ovary, and thyroid cancer, discussing carcinogenic activity of known EDCs, while evaluating the impact on public health. A literature review regarding EDCs and cancer was carried out with particular interest on meta-analysis and human studies. The definition of EDCs has been changed through years, and currently there are no common criteria to test new chemicals to clarify their possible carcinogenic activity. Moreover, it is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at different ages, even if preclinical and clinical evidence suggest that developing fetus and neonates are most vulnerable to endocrine disruption. EDCs represent a major environmental and health issue that has a role in cancer development. There are currently some EDCs that can be considered as carcinogenic, like dioxin and cadmium for breast and thyroid cancer; arsenic, asbestos, and dioxin for prostate cancer; and organochlorines/organohalogens for testicular cancer. New evidence supports the role of other EDCs as possible carcinogenic and pregnant women should avoid risk area and exposure. The relationship between EDCs and cancer supports the need for effective prevention policies increasing public awareness.

Environmental endocrine disruptors and amphibian immunity: A bridge between the thyroid hormone axis and T cell development

Immunity is susceptible to reprogramming by environmental chemical and endocrine signals. Notably, numerous thyroid disrupting chemicals (TDCs) have the potential to perturb immune endpoints, but data are lacking on the mechanisms by which TDCs can influence the development of the immune system. T cell immunity is particularly vulnerable to modulation by TDCs during thymic education, differentiation, and selection. The following review discusses the ways in which thyroid hormones may influence T cell development, as well as emerging TDCs with potential to impact both thyroid hormone physiology and immune outcomes. To overcome the challenges of studying TDC impacts on immune toxicological endpoints, a comparative approach using the amphibian Xenopus laevis is recommended. X. laevis are ideally suited to studying TDC impacts on immunity due to the importance of thyroid hormones for metamorphosis, and the wealth of immunological models to measure immune endpoints in both tadpoles and adult frogs.

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease.

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: •Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. •Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Neuropsychological side effects of combined hormonal contraceptives for the treatment of mild symptoms. Bioethical assessment of its adequacy

Since the beginning of the commercialization, in 1960, of combined estrogen-progestin hormonal contraceptives (CHCs), their use has become widespread for other non-contraceptive indications: dysmenorrhea, irregular cycle length, hypermenorrhea and acne, among others (Lete, 2009; Barranco, 2016). In all cases, these are mild pathologies or minor symptoms for which there are effective therapeutic alternatives. Millions of women in the world receive this treatment, which acts by inhibiting the hypothalamic-pituitary-ovarian hormonal axis (HHO Axis), the central axis and regulator of the entire sexual and reproductive physiology of women. Despite the existence of an enormous number of women subjected to this inhibition (ACHs are currently used by some 214 million women around the world, with an annual market of close to 18 billion dollars), very little research has been done on the consequences of suppressing the HHO axis. Only in recent years, and in parallel to the demonstration of the existence of functional receptors for gonadotropins at different levels in the central and peripheral nervous systems, have publications on the neuropsychological effects of HCAs begun to appear. It is also striking that, despite being the most widely used drugs and for the longest time for the treatment of functional gynecological disorders, their use is outside the technical data sheet (i.e., they are used for purposes other than those listed in the official indication approved in their technical data sheet and which appear in the package insert). Although the use of these hormonal products causes a wide variety of side effects, which have been widely studied in the medical literature, the present study proposes, after an exposition of the different aspects of the use of HCAs, a detailed review of the available literature on the neuropsychological effects due to the annulment of the HHO axis. This in order to, after a biological analysis, subsequently establish whether there is an ethical appropriateness in the use that concerns us.

Acute exposure to microcystins affects hypothalamic-pituitary axes of male rats

Microcystins (MCs) produced by some cyanobacteria can cause toxicity in animals and humans. In recent years, growing evidence suggests that MCs can act as endocrine disruptors. This research systematically investigated effects of microcystin-LR (MC-LR) on endocrine organs, biosynthesis of hormones and positive/negative feedback of the endocrine system in rats. Male, Sprague-Dawley rats were acutely administrated MC-LR by a single intraperitoneal injection at doses of 45, 67.5 or 90 μg MC-LR/kg body mass (bm), and then euthanized 24 h after exposure. In exposed rats, histological damage of hypothalamus, pituitary, adrenal, testis and thyroid were observed. Serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT), expressions of genes and proteins for biosynthesis of hormones were lesser, which indicated an overall suppression of the hypothalamus-pituitary-adrenal (HPA) axis. Along the hypothalamus-pituitary-gonadal (HPG) axis, lesser concentrations of gonadotropin-releasing hormone (GnRH) and testosterone (T), but greater concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were observed. Except for greater transcription of cyp19a1 in testes, transcriptions of genes and proteins for T and E2 biosynthesis along the HPG axis were lesser. As for the hypothalamus-pituitary-thyroid (HPT) axis, after MCs treatment, greater concentrations of thyroid-stimulating hormone (TSH), but lesser concentrations of free tri-iodothyronine (fT3) were observed in serum. Concentrations of free tetra-iodothyronine (fT4) were greater in rats dosed with 45 μg MCs/kg, bm, but lesser in rats dosed with 67.5 or 90 μg MCs/kg, bm. Transcripts of genes for biosynthesis of hormones and receptors along the HPT axis and expressions of proteins for biosynthesis of tetra-iodothyronine (T4) and tri-iodothyronine (T3) in thyroid were significantly altered. Cross-talk among the HPA, HPG and HPT axes probably occurred. It was concluded that MCs caused an imbalance of positive and negative feedback of hormonal regulatory axes, blocked biosynthesis of key hormones and exhibited endocrine-disrupting effects.

COVID-19: Some Pathophysiological and Endocrine Aspects

Summary The pandemic caused by COVID-19 infection almost two years ago is associated with many unknown multi-organ damages, including the endocrine system. Based on the fact that endocrine gland tissues express ACE-2 and TMPRSS2, it has been suggested that they may be directly attacked by the virus and cause toxic effects on them directly or indirectly by an autoimmune mechanism. Hypothalamic-pituitary-adrenal axis hormones are crucial for the course and progression of the disease and modulate the magnitude of the immune response and adaptation to stress. The aim of the present review is to summarize the state of the art in the COVID-19 and endocrine problems in its clinical and pathophysiological part and to answer the question of to what extent patients with COVID-19 have a higher risk of adverse outcomes.

Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis – A post-hoc cohort study of the HMB-ICU trial

β-hydroxy-β-methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D. Post-hoc analysis of the study HMB-ICU, a randomized, placebo-controlled double-blind trial. Intensive care unit (ICU) patients depending on mechanical ventilation on day 3 with functional gastrointestinal tract. Patients were randomized to HMB (3g/day) or placebo (maltodextrin) from day 4 on, for 30 days. Blood samples were collected on days 4 and 15. We determined the GH, C-peptide, 25-OH vitamin-D, and IGF-1. Statistics by ANCOVA. Blood samples of 26 patients were available on day 4, and 23 on day 15. While age and severity of disease did not differ, diabetes was more frequent in the HMB group (p=0.041), and obesity was more frequent in the placebo group (p=0.021). Glucose intake, blood glucose (BG) and amount of insulin to maintain blood glucose between 6 and 8mM did not differ between groups. There was no difference between groups for C-peptide, GH, IGF-1, and 25-OH vitamin-D. IGF-1 increased significantly from day 4-15 (p=0.026) in both groups. Subject to possible insufficient power of the study, we did not reach conclusive results. HMB intervention does not affect significantly the plasma concentrations of insulin, GH/IGF axis activity, C-peptide, and 25-OH vitamin-D. NCT03628365.

Metabolic and hormonal changes after laparoscopic sleeve gastrectomy in pediatric population: An observational study.

Despite the growing popularity of laparoscopic sleeve gastrectomy (SG) for managing severe obesity in children, adolescents, and adults, there is a paucity of studies reporting the effects of SG on metabolic and hormonal outcomes in pediatric populations. In this single-centre, retrospective study, we assessed nutritional biomarkers (hemoglobin, ferritin, iron profile, Vitamin B12, Vitamin D, and calcium), glucose homeostasis indicators (C-peptide, HbA1C, and random blood glucose), blood lipids (triglycerides and cholesterol components), hormones involved in the hypothalamic-pituitary-adrenal axis (cortisol and adrenocorticotropic hormone), and thyroid hormones (T3, T4, thyroid-stimulating hormone, and parathyroid hormone) preoperatively and 12-month after SG in children aged 5-15 years. This study included 64 adolescents (mean age = 11.2 ± 2.3 years) who underwent laparoscopic SG. Significant reduction in circulatory C-peptide (-62.1%; p = 0.005), HbA1C (-10.9%; p = 0.001), random blood glucose (-15.4%; p = 0.036), and triglycerides (-39.4%; p = 0.003) were observed postoperatively at 12 months compared to baseline. Although we did not observe any changes in cortisol levels, adrenocorticotropic hormone levels declined significantly by -40.9% postoperatively (p = 0.033). However, cholesterol components, thyroid hormones, and nutritional biomarkers remained unchanged from baseline. Consistent with prior literature, our study demonstrates improvement or resolution of diabetes and hypertriglyceridemia in the year following SG. However, given that blood cholesterol components, nutritional biomarkers, and thyroid profiles remained unchanged warrants long-term monitoring of nutritional, metabolic, and endocrine factors in adolescents undergoing laparoscopic SG. To the best of our knowledge, this is the first study reporting the effects of SG on thyroid and hypothalamic-pituitary-adrenal axis hormones in pediatric populations.

Changes in pathophysiology of tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis in rats of both sexes with the development of Guerin's carcinoma on the background of hypothyroidism

Purpose of the study. Was to analyze changes in pathophysiological parameters of transplantable tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis (HPT) in rats of both sexes with Guerin's carcinoma in presence of induced hypothyroidism.Materials and methods. The dynamics of tumor growth and average life span were assessed in white alley rats of both sexes with Guerins carcinoma transplanted subcutaneously on the background of thyreostatic induced hypothyroidism. RIA (radioimmune assay) and ELISA (enzyme-linked immunosorbent assay) methods were used to determine levels of thyroid hormones in the blood and thyroid and tumor samples, and thyrotropin-releasing hormone (TRH) in the hypothalamus, as well as TSH in the pituitary gland. The experiment included 2 control groups: animals of both sexes with hypothyroidism (control group 1, number of rodents = 15) and animals with subcutaneously transplanted Guerin's carcinoma without hypothyroidism (control group 2, number of rodents = 15).Results. Hypothyroidism in female rats inhibited the tumor growth and improved median survival by 1.8 times (p &lt; 0.05). No such effect was observed in males of the main group. Levels of regulatory peptides of the hypothalamus and pituitary gland declined in females of the main group, while levels of TSH in the pituitary gland in males increased, despite a decrease in TRH by 3.5 times. TSH levels decreased in the thyroid and blood of animals of both sexes; however, a decrease in levels of total and free circulating thyroxine (T4 and FT4) by 1.6 times and by 2.8 times was found in the tumor, respectively; samples of Guerin's carcinoma in males of the main group remained saturated with T4 and FT4 as well as and in control group rodents without induced hypothyroidism.Conclusions. The gender differences in the pathophysiology of the tumor development in presence of hypothyroidism, as well as changes in the functional activity of the HPT axis in experimental animals revealed in this study can probably be associated with sex hormones, which requires further study of the hypothalamic-pituitary-gonadal (HPG) axis and steroid hormones in peripheral organs and tumor samples.

Associations of GHR, IGF-1 and IGFBP-3 expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP) regulate growth and metabolic pathways. Using our Leipzig Adipose Tissue (AT) Childhood Cohort and Leipzig Atherobesity Childhood Cohort (n=306), we asked if serum levels of these factors are altered with overweight/obesity and if this is related to gene expression of these factors in AT cells and/or increased fat mass in childhood obesity. Furthermore, we hypothesized that gene expression of GHR, IGF-1 and IGFBP-3 in AT is associated with overweight/obesity and AT function in children. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio this obesity-related elevation was only detectable until early puberty. Circulating levels did not correlate with gene expression of these factors in AT cells, which was decreased with overweight/obesity. Independent from body mass index, gene expression of GHR, IGF-1 and IGFBP-3 in AT cells was related to parameters of AT dysfunction, such as adipocyte hypertrophy, and increased insulin levels. Serum GHBP was associated with the percentage of liver fat and transaminase levels. We conclude that the obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased subcutaneous AT mass and elevations in serum GHBP are more closely related to liver status in children. The diminished gene expression of these factors in AT cells with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.