Hormone Axis Research Articles

Insulin-like growth factor-1 (Igf1) signaling responses to food consumption after fasting in the Pacific rockfish Sebastes carnatus

Fish adjust rates of somatic growth in the face of changing food consumption. As in other vertebrates, growth in fish is regulated by the growth hormone (Gh)/insulin-like growth factor-1 (Igf1) endocrine axis, and changes in food intake impact growth via alterations to Gh/Igf1 signaling. Understanding the time course by which the Gh/Igf1 axis responds to food consumption is crucial to predict how rapidly changes in food abundance might lead to altered growth dynamics. Here, we looked at the response times of plasma Igf1 and liver Igf1 signaling-associated gene expression to refeeding after food deprivation in juvenile gopher rockfish (Sebastes carnatus), one of several species of northern Pacific Ocean Sebastes rockfishes targeted by fisheries or utilized for aquaculture. Gopher rockfish were fasted for 30 d, after which a subset was fed to satiation for 2 h, while other rockfish continued to be fasted. Refed fish exhibited higher hepatosomatic index (HSI) values and increased Igf1 after food consumption. Gene transcripts for Gh receptor 1 (ghr1), but not ghr2, increased in the liver 2-4 d after eating. Transcripts encoding igf1also increased in the liver of refed fish by 4 d after feeding, only to return to levels similar as continually fasted rockfish by 9 d after feeding. Liver mRNA abundances for Igf binding protein (Igfbp) genes igfbp1a, igfbp1b, and igfbp3a declined within 2 d of feeding. These findings provide evidence that circulating Igf1 in rockfish reflects a fish's feeding experience within the previous few days, and suggest that feeding-induced increases in Igf1 are being mediated in part by altered liver sensitivity to Gh due to upregulated Gh receptor 1 expression.

Reproductive toxicity of combined effects of endocrine disruptors on human reproduction.

Confluence of environmental, genetic, and lifestyle variables is responsible for deterioration of human fecundity. Endocrine disruptors or endocrine disrupting chemicals (EDCs) may be found in a variety of foods, water, air, beverages, and tobacco smoke. It has been demonstrated in experimental investigations that a wide range of endocrine disrupting chemicals have negative effects on human reproductive function. However, evidence on the reproductive consequences of human exposure to endocrine disrupting chemicals is sparse and/or conflicting in the scientific literature. The combined toxicological assessment is a practical method for assessing the hazards of cocktails of chemicals, co-existing in the environment. The current review provides a comprehensive overview of studies emphasizing the combined toxicity of endocrine disrupting chemicals on human reproduction. Endocrine disrupting chemicals interact with each other to disrupt the different endocrine axes, resulting in severe gonadal dysfunctions. Transgenerational epigenetic effects have also been induced in germ cells, mostly through DNA methylation and epimutations. Similarly, after acute or chronic exposure to endocrine disrupting chemicals combinations, increased oxidative stress (OS), elevated antioxidant enzymatic activity, disrupted reproductive cycle, and reduced steroidogenesis are often reported consequences. The article also discusses the concentration addition (CA) and independent action (IA) prediction models, which reveal the importance of various synergistic actions of endocrine disrupting chemicals mixtures. More crucially, this evidence-based study addresses the research limitations and information gaps, as well as particularly presents the future research views on combined endocrine disrupting chemicals toxicity on human reproduction.

Alterations in serum Thyroid and Reproductive hormone levels in occupationally exposed pesticides sprayers

Background: Pesticides contain endocrine disrupting chemicals that have potential to perturb the normal thyroid and reproductive hormone axis. The aim of present study was to estimate the variations in serum tri-iodothyronine (T3) tetra-iodothyronine (T4) thyroid stimulating hormone (TSH) and testosterone levels in occupationally exposed pesticide sprayers in comparison to controls.
 Methods: For this purpose, blood samples of (n=50) pesticide sprayers were collected from District Layyah, south Punjab, Pakistan. Whereas, samples (n=25) of healthy control subjects were obtained from University of the Punjab, Lahore. Levels of T3, T4, TSH and testosterone in the serum were estimated by ELISA technique. The data obtained was analyzed by applying Un-paired Student “t” test at with significance level of P < 0.05. Graph pad prism version 6.0 software was utilized for statistical interpretation.
 Results: Pronounced (P < 0.0001) decrease of both T3 and T4, whereas, a significant increase in TSH (P = 0.005) level was evidenced in pesticide sprayers as compared to controls. Moreover, a significant decrease (P < 0.001) was noted in the level of testosterone in pesticide sprayers as compared to controls.
 Conclusion: Pertinently, the pesticides are a potent source of inducing imbalances in T3, T4, TSH, and testosterone secretion. Pesticide sprayers are, therefore, recommended to use prophylactic measures like wearing face masks and opt safer protocols in order to avoid direct hazardous exposure to endocrine disrupting chemicals.

Urinary concentration of phthalates and bisphenol A during minipuberty is associated with reproductive hormone concentrations in infant boys.

The transient postnatal activation of the hypothalamic-pituitary-gonadal hormone axis is termed minipuberty and considered an important developmental period, which is highly sensitive to endocrine disruption. Here, we explore exposure-outcome associations during minipuberty between concentrations of potentially endocrine disrupting chemicals (EDCs) in urine of infant boys and their serum reproductive hormone concentrations. In total, 36 boys participating in the COPENHAGEN Minipuberty Study had data available for both urine biomarkers of target endocrine disrupting chemicals and reproductive hormones in serum from samples collected on the same day. Serum concentrations of reproductive hormones were measured by immunoassays or by LC-MS/MS. Urinary concentrations of metabolites of 39 non-persisting chemicals, including phthalates and phenolic compounds, were measured by LC-MS/MS. Nineteen chemicals had concentrations above the limit of detection in ≥50% of children and were included in data analysis. Associations of urinary phthalate metabolite and phenol concentrations (in tertiles) with hormone outcomes (age- and sex-specific SD-scores) were analysed by linear regression. Primarily, we focused on the EU regulated phthalates; butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-(2-ethylhexyl) phthalate (DEHP) as well as bisphenol A (BPA). Urinary metabolites of DiBP, DnBP and DEHP were summed and expressed as ∑DiBPm, ∑DnBPm and ∑DEHPm. Compared to boys in the lowest ∑DnBPm tertile, urinary concentration of ∑DnBPm was associated with concurrent higher luteinizing hormone (LH) and anti-Müllerian hormone (AMH) SD-scores as well as lower testosterone/LH ratio in boys in the middle ∑DnBPm tertile (estimates (CI 95%) 0.79 (0.04; 1.54), 0.91 (0.13; 1.68), and -0.88 (-1.58;-0.19), respectively). Further, higher insulin-like peptide 3 (INSL3) SD-scores and lower DHEAS SD-score in boys in the highest ∑DnBPm tertile (0.91 (0.12; 1.70) and -0.85 (-1.51;-0.18), respectively) were observed. In addition, boys in the middle and highest ∑DEHPm tertile had higher LH (1.07 (0.35; 1.79) and 0.71 (-0.01; 1.43), respectively) and in the highest ∑DEHPm tertile also higher AMH (0.85 (0.10; 1.61)) concentration SD-scores, respectively. Boys in the highest BPA tertile had significantly higher AMH and lower DHEAS concentration compared to boys in the lowest BPA tertile (1.28 (0.54; 2.02) and -0.73 (-1.45; -0.01)), respectively. Our findings indicate that exposure to chemicals with known or suspected endocrine disrupting potential, especially the EU-regulated DnBP, DEHP and BPA, may modify male reproductive hormone concentrations in infant boys suggesting that minipuberty is a critical window sensitive to endocrine disruption.

Dynamics of Delayed Neuroendocrine Systems and Their Reconstructions Using Sparse Identification and Reservoir Computing

Neuroendocrine system mainly consists of hypothalamus, anterior pituitary, and target organ. In this paper, a three-state-variable delayed Goodwin model with two Hill functions is considered, where the Hill functions with delays denote the hormonal feedback suppressions from target organ to hypothalamus and to anterior in the reproductive hormonal axis. The existence of Hopf bifurcation shows the circadian rhythms of neuroendocrine system. The direction and stability of Hopf bifurcation are also analyzed using the normal form theory and the center manifold theorem for functional differential equations. Furthermore, based on the sparse identification algorithm, it is verified that the transient time series generated from the delayed Goodwin model cannot be equivalently presented by ordinary differential equations from the viewpoint of data when considering that a library of candidates are at most cubic terms. The reason is because the solution space of delayed differential equations is of infinite dimensions. Finally, we report that reservoir computing can predict the periodic behaviors of the delayed Goodwin model accurately if the size of reservoir and the length of data used for training are large enough. The predicting performances are evaluated by the mean squared errors between the trajectories generated from the numerical simulations and the reservoir computing.

Abstract #1412022: A Rare Case of Multiple Endocrine Neoplasia Type 1 (MEN1) Presenting with Recurrent Abdominal Pain

MEN1 is a rare genetic disorder characterized by combined occurrence of two or more tumors involving parathyroid, anterior pituitary and the neuroendocrine tissue of gastro-entero-pancreatic organ system. We present a case of a young male with recurrent abdominal pain who was later diagnosed with MEN1 syndrome. 27-year-old male with past medical history of chronic abdominal pain presented for an episode of acute upper abdominal pain which was constant and worsened with any movement or palpation. His family history was significant for father having parathyroid disorder and skin lesions. On examination, he was ill appearing with tachycardia, multiple skin lesions and tenderness in upper abdomen. Labs were significant for leukocytosis and hypercalcemia (corrected level 10.5 mg/dl). Rest of the electrolytes, kidney function, liver enzymes and lipase were normal. Computed tomography (CT) abdomen showed inflammatory changes and thickening along the distal stomach/proximal duodenum with scattered free air, concerning for a perforated ulcer. Indeterminate bilateral adrenal nodules were also noted. Patient underwent emergent exploratory laparotomy and was noted to have small perforation in the anterior proximal portion of the duodenum which was repaired. Post-operatively, work up for persistent hypercalcemia revealed parathyroid hormone levels of 152 pg/ml and 25-hydroxy vitamin D of 13.7 ng/ml. He was diagnosed with primary hyperparathyroidism and upon stabilization, discharged with plan for outpatient follow-up. After few months, he had another admission due to worsening epigastric pain. Repeat CT abdomen showed multiple pancreatic lesions involving head, tail and uncinate process and stable adrenal nodules. Presence of pancreatic lesions, gastric ulcers, hyperparathyroidism, adrenal nodules, and multiple skin lesions raised concern of MEN1. Further evaluation showed elevated gastrin level (633 pg/ml), chromogranin level (2464 ng/mL) and mildly elevated prolactin. Rest of pituitary and adrenal axis hormone levels were normal. MEN1 gene testing was positive. No pituitary lesion was identified on magnetic resonance imaging brain. He underwent subtotal parathyroidectomy and cervical thymectomy. He was continued on twice daily pantoprazole and was discharged home in stable condition. MEN1 tumor types and age of tumor onset can differ significantly, and tumors become evident either by hormonal overproduction or by tumor growth. There are no genotype phenotype correlations, even within the same family. Pharmacological therapies to suppress hypersecretion are often first line and can be successful in up to 50% patients. Surgery is an option for patients with hypersecretion unresponsive to medical therapy, compression of the optic nerves and/or chiasma endangering vision or when there is uncertainty of diagnosis requiring biopsy. MEN1 is linked with higher mortality. Approximately 70% of the MEN1 deaths are due to thymic neuroendocrine tumors (NETs) and duodenopancreatic-NETs. Early diagnosis of tumors with appropriate interventions can significantly improve patient survival.

Abstract #1406483: Thyroid Hormone Resistance Diagnostic and Therapeutic Challenges

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH). We present the challenges in diagnosing and treating a 24-year-old male who presented with a mixed picture of hypothyroidism and hyperthyroidism with elevated TSH, upper normal free T4, and elevated free T3 and was found to have a mutation in the THRβ gene. A 24-year-old male was referred for a second opinion of post-ablative hypothyroidism with elevated TSH, elevated free T3, and suspicion of pituitary microadenoma. He complained of fatigue, weight gain, tremors heat cold intolerance. Family history is Graves’ disease in his mother's status post partial thyroidectomy due to a salivary tumor. Initially, in 2020, he was diagnosed with negative antibody Grave’s disease. Labs were TSH 0.86 mIU/L, free T4 1.99 ng/dl (0.89-1.76), and free T3 4.66 pg/ml (2.3-4.2). A thyroid ultrasound showed mild thyromegaly. A thyroid uptake scan showed 24-hour thyroid uptake of 36.7%. Thyroid antibodies including thyroglobulin, TPO, thyroid receptor, and thyroid stimulating immunoglobulin were negative. He was treated with radioactive iodine ablation (I-131). Afterward, His TSH increased gradually along with free T3. Free T4 was normal. The patient remained symptomatic, and he was not on any thyroid replacement therapy. A repeat thyroid uptake scan showed an increase uptake of 36% at 24 hrs. During our evaluation, a repeat TSH 54.05 mIU/l, free T4 1.3 ng/dl, free T3 4.3 pg/ml, and T3 by equilibrium dialysis 4.0. A repeat magnetic resonance imaging of the head showed no definitive focal enhancing lesion. Pituitary axis hormones were normal, and the alpha subunit was 0.73 (high); however, the alpha-glycoprotein subunit /TSH molar ratio 0.135 sex hormone binding globulin 5.8 nmol/l (low), macro TSH was not detected. These findings raised suspicion for THRB mutation; hence genetic studies were obtained. PCR amplification of THRB gene exons 10, 9, and 8, followed by gene sequencing, showed a heterozygous missense mutation C >G located at exon 10. The mutation caused a change in thyroid hormone receptor beta protein amino acid 453 proline to an alanine, P453A Initially, he was started on levothyroxine 25 mg PO daily but soon after, it was stopped due to palpitations; a beta blocker was started along with liothyronine 5 mg every other day and levothyroxine 50 mg every other day. The patient tolerated the regimen with significant improvement in his symptoms. RTH is rather uncommon; it is important to be able to recognize the syndrome to avoid unnecessary invasive treatment. There is no specific therapy currently available to fully correct the TRβ defect. The goal of treatment is based on the patient's symptoms and clinical picture instead of aiming to normalize thyroid hormone levels. Thyroidectomy and radioactive iodine ablation result in lifelong levothyroxine replacement therapy and RTHβ persistently high serum TSH. Levothyroxine therapy is challenging, and supraphysiologic doses are often needed to maintain serum TSH in the lowest tolerable level.

Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling.

There is high clinical demand for the resolution of tendinopathies, which affect mainly adult individuals and animals. Tendon damage resolution during the adult lifetime is not as effective as in earlier stages where complete restoration of tendon structure and property occurs. However, the molecular mechanisms underlying tendon regeneration remain unknown, limiting the development of targeted therapies. The research aim was to draw a comparative map of molecules that control tenogenesis and to exploit systems biology to model their signaling cascades and physiological paths. Using current literature data on molecular interactions in early tendon development, species-specific data collections were created. Then, computational analysis was used to construct Tendon NETworks in which information flow and molecular links were traced, prioritized, and enriched. Species-specific Tendon NETworks generated a data-driven computational framework based on three operative levels and a stage-dependent set of molecules and interactions (embryo-fetal or prepubertal) responsible, respectively, for signaling differentiation and morphogenesis, shaping tendon transcriptional program and downstream modeling of its fibrillogenesis toward a mature tissue. The computational network enrichment unveiled a more complex hierarchical organization of molecule interactions assigning a central role to neuro and endocrine axes which are novel and only partially explored systems for tenogenesis. Overall, this study emphasizes the value of system biology in linking the currently available disjointed molecular data, by establishing the direction and priority of signaling flows. Simultaneously, computational enrichment was critical in revealing new nodes and pathways to watch out for in promoting biomedical advances in tendon healing and developing targeted therapeutic strategies to improve current clinical interventions.

Effects of chronic dichlorodiphenyldichloroethylene exposure on testosterone secretion and steroidogenic pathway in the male gonad.

Endocrine disrupting chemicals are present in the environment and/or in consumer products. These agents have the capacity to mimic and/or antagonize endogenous hormones and thus perturb the endocrine axis. The male reproductive tract expresses steroid hormone (androgen and estrogen) receptors at high levels and is a major target for endocrine disrupting chemicals. In this study, Long-Evans male rats were exposed to dichlorodiphenyldichloroethylene, a metabolite of dichlorodiphenyltrichloroethane and a chemical present in the environment, in drinking water at 0.1 and 10μg/L for 4 weeks. At the end of exposure, we measured steroid hormone secretion and analyzed steroidogenic proteins, including 17β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, steroidogenic acute regulatory protein, aromatase, and the LH receptor. We also analyzed Leydig cell apoptosis (poly-(ADP-ribose) polymerase) and caspase-3 in the testes. Testicular testosterone (T) and 17β-estradiol (E2) were both affected by exposure to dichlorodiphenyldichloroethylene by displaying altered steroidogenic enzyme expression. Dichlorodiphenyldichloroethylene exposure also increased the expression of enzymes mediating the pathway for programmed cell death, including caspase 3, pro-caspase 3, PARP, and cleaved PARP. Altogether, the present results demonstrate that dichlorodiphenyldichloroethylene directly and/or indirectly can target specific proteins involved in steroid hormone production in the male gonad and suggest that exposure to environmentally relevant dichlorodiphenyldichloroethylene levels has implications for male reproductive development and function.

Gonadotropin axis and semen quality in young Swiss men after cannabis consumption: Effect of chronicity and modulation by cannabidiol.

While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus-pituitary-gonadotropic axis. To assess the impact of the consumption of Δ-9-tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men. The individuals in a Swiss cohort were divided according to their cannabis consumption. In the cannabis user group, we determined the delay between the last intake of cannabis and sample collection, the chronicity of use and the presence of cannabidiol in the consumed product. Urinary Δ-9-tetrahydrocannabinol metabolites were quantified via gas chromatography-mass spectrometry. Blood phytocannabinoids, endocannabinoids and male steroids were determined via liquid chromatography-mass spectrometry/mass spectrometry, and other hypothalamus-pituitary-gonadotropic axis hormones were determined via immunoassays. Semen parameters such as sperm concentration and motility were recorded using computer-assisted sperm analysis. Anandamide, N-palmitoyl ethanolamide, androgens, estradiol and sex hormone binding globulin levels were all higher in cannabis users, particularly in chronic, recent and cannabidiol-positive consumers. Gonadotropin levels were not significantly different in these user subpopulations, whereas prolactin and albumin concentrations were lower. In addition, cannabis users had a more basic semen pH and a higher percentage of spermatozoa with progressive motility. However, the two latter observations seem to be related to a shorter period of sexual abstinence in this group rather than to the use of cannabis. Because both cannabidiol and Δ-9-tetrahydrocannabinol are frequently used by men of reproductive age, it is highly relevant to elucidate the potential effects they may have on human reproductive health. This study demonstrates that the mode of cannabis consumption must be considered when evaluating the effect of cannabis on semen quality.

Insights on the NF-κB system in polycystic ovary syndrome, attractive therapeutic targets.

The nuclear factor κappa B (NF-κB) signaling plays a well-known function in inflammation and regulates a wide variety of biological processes. Low-grade chronic inflammation is gradually considered to be closely related to the pathogenesis of Polycystic ovary syndrome (PCOS). In this review, we provide an overview on the involvement of NF-κB in the progression of PCOS particularly, such as hyperandrogenemia, insulin resistance, cardiovascular diseases, and endometrial dysfunction. From a clinical perspective, progressive recognition of NF-κB pathway provides opportunities for therapeutic interventions aimed at inhibiting pathway-specific mechanisms. With the accumulation of basic experimental and clinical data, NF-κB signaling pathway was recognized as a therapeutic target. Although there have been no specific small molecule NF-κB inhibitors in PCOS, a plethora of natural and synthetic compound have emerged for the pharmacologic intervention of the pathway. The traditional herbs developed for NF-κB pathway have become increasingly popular in recent years. Abundant evidence elucidated that NF-κB inhibitors can significantly improve the symptoms of PCOS. Herein, we summarized evidence relating to how NF-κB pathway is involved in the development and progression of PCOS. Furthermore, we present an in-depth overview of NF-κB inhibitors for therapy interventions of PCOS. Taken together, the NF-κB signaling may be a futuristic treatment strategy for PCOS.

Hypothalamus-pituitary-interrenal (HPI) axis signaling in Atlantic sturgeon (Acipenser oxyrinchus) and sterlet (Acipenser ruthenus)

In vertebrates, the hypothalamic–pituitaryadrenal/interrenal (HPA/HPI) axis is a highly conserved endocrine axis that regulates glucocorticoid production via signaling by corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). Once activated by ACTH, Gs protein-coupled melanocortin 2 receptors (Mc2r) present in corticosteroidogenic cells stimulate expression of steroidogenic acute regulatory protein (Star), which initiates steroid biosynthesis. In the present study, we examined the tissue distribution of genes involved in HPI axis signaling and steroidogenesis in the Atlantic sturgeon (Acipenser oxyrinchus) and provided the first functional characterization of Mc2r in sturgeon. Mc2r of A. oxyrinchus and the sterlet sturgeon (Acipenser ruthenus) are co-dependent on interaction with the melanocortin receptor accessory protein 1 (Mrap1) and highly selective for human (h) ACTH over other melanocortin ligands. A. oxyrinchus expresses key genes involved in HPI axis signaling in a tissue-specific manner that is indicative of the presence of a complete HPI axis in sturgeon. Importantly, we co-localized mc2r, mrap1, and star mRNA expression to the head kidney, indicating that this is possibly a site of ACTH-mediated corticosteroidogenesis in sturgeon. Our results are discussed in the context of other studies on the HPI axis of basal bony vertebrates, which, when taken together, demonstrate a need to better resolve the evolution of HPI axis signaling in vertebrates.

Involvement of Dmp1 in the Precise Regulation of Hair Bundle Formation in the Developing Cochlea.

Dentin matrix protein 1 (Dmp1) is a highly phosphorylated, extracellular matrix protein that is extensively expressed in bone and teeth but also found in soft tissues, including brain and muscle. However, the functions of Dmp1 in the mice cochlea are unknown. Our study showed that Dmp1 was expressed in auditory hair cells (HCs), with the role of Dmp1 in those cells identified using Dmp1 cKD mice. Immunostaining and scanning electron microscopy of the cochlea at P1 revealed that Dmp1 deficiency in mice resulted in an abnormal stereociliary bundle morphology and the mispositioning of the kinocilium. The following experiments further demonstrated that the cell-intrinsic polarity of HCs was affected without apparent effect on the tissue planer polarity, based on the observation that the asymmetric distribution of Vangl2 was unchanged whereas the Gαi3 expression domain was enlarged and Par6b expression was slightly altered. Then, the possible molecular mechanisms of Dmp1 involvement in inner ear development were explored via RNA-seq analysis. The study suggested that the Fgf23-Klotho endocrine axis may play a novel role in the inner ear and Dmp1 may regulate the kinocilium-stereocilia interaction via Fgf23-Klotho signaling. Together, our results proved the critical role of Dmp1 in the precise regulation of hair bundle morphogenesis in the early development of HCs.

The Overview of Menstrual Physiology: A Narrative Literature Review

Menstruation is a physiological or normal condition, namely events of the production of blood, mucus, and cell waste periodically originate from the uterine mucosa and occur relatively regularly from menarche until menopause, except during pregnancy and lactation. Menstruation is the result of very neat and standard cooperation from the hypothalamus-pituitary-ovarian endocrine axis. Hypothalamus spurs the pituitary gland by secreting gonadotropin-releasing hormone (GnRH), a deca-peptide secreted pulsatively by the hypothalamus. Menstruation is considered normal if it occurs between 22-35 days. Disturbance menstruation is most common at the beginning and end of the reproductive period, namely in those under 19 years of age and over 39 years of age. These disturbances may be related to the length of the menstrual cycle or the number and duration of menstruation. One person Women can experience both disorders. This literature review aimed to describe the menstrual cycle physiologically and the disorders that accompany it.

Ginkgolide B facilitates muscle regeneration via rejuvenating osteocalcin-mediated bone-to-muscle modulation in aged mice.

The progressive deterioration of tissue-tissue crosstalk with aging causes a striking impairment of tissue homeostasis and functionality, particularly in the musculoskeletal system. Rejuvenation of the systemic and local milieu via interventions such as heterochronic parabiosis and exercise has been reported to improve musculoskeletal homeostasis in aged organisms. We have shown that Ginkgolide B (GB), a small molecule from Ginkgo biloba, improves bone homeostasis in aged mice by restoring local and systemic communication, implying a potential for maintaining skeletal muscle homeostasis and enhancing regeneration. In this study, we investigated the therapeutic efficacy of GB on skeletal muscle regeneration in aged mice. Muscle injury models were established by barium chloride induction into the hind limb of 20-month-old mice (aged mice) and into C2C12-derived myotubes. Therapeutic efficacy of daily administrated GB (12mg/kg body weight) and osteocalcin (50μg/kg body weight) on muscle regeneration was assessed by histochemical staining, gene expression, flow cytometry, ex vivo muscle function test and rotarod test. RNA sequencing was used to explore the mechanism of GB on muscle regeneration, with subsequent in vitro and in vivo experiments validating these findings. GB administration in aged mice improved muscle regeneration (muscle mass, P=0.0374; myofiber number/field, P=0.0001; centre nucleus, embryonic myosin heavy chain-positive myofiber area, P=0.0144), facilitated the recovery of muscle contractile properties (tetanic force, P=0.0002; twitch force, P=0.0005) and exercise performance (rotarod performance, P=0.002), and reduced muscular fibrosis (collagen deposition, P<0.0001) and inflammation (macrophage infiltration, P=0.03). GB reversed the aging-related decrease in the expression of osteocalcin (P<0.0001), an osteoblast-specific hormone, to promote muscle regeneration. Exogenous osteocalcin supplementation was sufficient to improve muscle regeneration (muscle mass, P=0.0029; myofiber number/field, P<0.0001), functional recovery (tetanic force, P=0.0059; twitch force, P=0.07; rotarod performance, P<0.0001) and fibrosis (collagen deposition, P=0.0316) in aged mice, without an increased risk of heterotopic ossification. GB treatment restored the bone-to-muscle endocrine axis to reverse aging-related declines in muscle regeneration and thus represents an innovative and practicable approach to managing muscle injuries. Our results revealed the critical and novel role of osteocalcin-GPRC6A-mediated bone-to-muscle communication in muscle regeneration, which provides a promising therapeutic avenue in functional muscle regeneration.

Medications affecting the insulin-like growth factor 1/growth hormone axis, including teprotumumab, somatostatin analogs, and anti-calcitonin gene-related peptide monoclonal antibodies, are associated with elevated reporting odds of alopecia in women: A pharmacovigilance study

Medications affecting the insulin-like growth factor 1/growth hormone axis, including teprotumumab, somatostatin analogs, and anti-calcitonin gene-related peptide monoclonal antibodies, are associated with elevated reporting odds of alopecia in women: A pharmacovigilance study

ART outcomes of patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

BackgroundIsolated Hypogonadotropic Hypogonadism (IHH) is a rare reproductive disorder caused by the dysfunction of the gonadotropin-releasing hormone axis. Patients with IHH typically fail to enter or develop through puberty and retain infertile without an exogenous hormone supplement. This study aimed to investigate the population characteristics and reproductive outcomes in IHH patients undergoing assisted reproductive technology (ART) treatment, and evaluate the best-performed predictor for ovarian response and clinical pregnancy in patients with IHH.MethodsThis retrospective cohort study included 83 women with IHH who underwent fresh ART cycles and non-diagnosed controls (n = 676). The receiver operating characteristic curves were generated to assess the predictor for the ovarian response. Logistic regression analyses were performed to investigate the independent factors for clinical pregnancy in IHH.ResultsThe basal hormone levels were significantly lower in the IHH group compared to the control group. The fertilization rate and 2PN rate were significantly higher in IHH groups, as was the number of transferable embryos. The study identified that AMH was the best predictor of high ovarian response in IHH, with an AUC of 0.767 (0.573, 0.961). Conversely, the follicle-to-oocyte index (FOI) exhibited the highest AUC of 0.814 (0.642, 0.985) for predicting low ovarian response. Based on FOI values, the IHH patients were divided into two groups, and the study found a significant increase in clinical pregnancy rate (43.8%, 58%; P < 0.001) and live birth rate (37.5%, 58%; P < 0.001) from the low FOI to the normal FOI groups. Moreover, the number of oocytes retrieved, fertilized embryos/rate, 2PN embryos/rate, and number of excellent quality embryos were significantly higher in the normal FOI group (P < 0.001 or P = 0.005) than in the low FOI group. Logistic regression analyses revealed FOI to be the independent factor affecting clinical pregnancy in IHH patients.ConclusionsThe study findings suggest that patients with IHH were good responders to IVF treatment. Although AMH was the best-performed predictor for the high ovarian response, FOI had the best capability in predicting the low ovarian response. FOI was an independent factor affecting clinical pregnancy in IHH undergoing IVF/ICSI.

Higher thyroid hormone has a negative association with lower limb lean body mass in euthyroid older adults: Analysis from the Baltimore Longitudinal study of aging.

Background: Hyperthyroidism is associated with lower lean body mass, as a result of catabolic actions of thyroid hormone. Therefore, higher thyroid hormone levels could be a factor in the development of sarcopenia and age associated functional decline. The relationship between thyroid hormone and muscle mass in ambulatory, euthyroid older adults is not known. Method: We used mixed-effects models to estimate the cross-sectional relationships (accounting for inter-person variability) between thyroid axis hormone measures and lower limb composition or sarcopenia at visits in the Baltimore Longitudinal Study of Aging (BLSA) at which DEXA scans were available and both thyrotropin (TSH) and free thyroxine (FT4) were in the reference range. Analyses were adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, cholesterol, and systolic blood pressure. Results: 1442 euthyroid participants (median age 68, 50% female, and 69% white) contributed to 5306 visits from 2003 to 2019. FT4 was negatively associated with lower limb lean mass (beta: 88.49; 95% Confidence Interval (CI): 122.78, -54.20; p < 0.001) and positively associated with sarcopenia (OR: 1.11%, 95% CI: 1.01, 1.22) in the whole cohort. Additionally, higher FT4 was associated with lower leg lean mass (beta: 66.79; 95% CI: 102.24, -31.33; p < 0.001) and sarcopenia (OR:1.09%, 95% CI:1.01, 1.18) in older adults, but not in younger adults alone. Conclusion: In euthyroid older adults, higher FT4 is associated with lower leg lean mass and higher odds of sarcopenia. Understanding the relationship between thyroid hormone and sarcopenia is needed to improve clinical decision-making and avoid functional decline from excess thyroid hormone use in older adults.

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Hormonal predictors of circulatory diseases in liquidators of Chernobyl accident consequences

Relevance. Diseases of the circulatory system occupy a leading place in the structure of somatic pathology of liquidators. Obesity, signs of asthenization, vegetal vascular disorders, which were detected in numerous studies, suggest the presence of hypogonadism in this category of victims. Sex hormone deficiency is considered an important link in the formation of non-communicable diseases, which determined the relevance of the study.The goal. To carry out a retrospective assessment of the change in the hormonal indicators of the endocrine axis of hypophysis-sex hormones and to assess the effect of partial androgen deficiency on the formation of circulatory diseases in the dynamics of the examination in the liquidators of the consequences of the Chernobyl accident.Materials and methods. Hormonal indicators of the pituitary-gonadal endocrine axis were investigated by immunochemical analysis in 1065 men involved in the aftermath of the Chernobyl accident in 1986–1987, combined into groups depending on the period of examination from 1994 to 2019 and in control groups. The average age of patients entering the Chernobyl zone was 33.6 (0.8) years.Results. Seven years after the accident, liquidators in 13.1 % cases show a shortage of sex hormones, by 33 years of follow-up, the proportion of such patients increases by 4.6 times. Sex hormone deficiency 7 years after the accident was revealed in men of relatively young age, the correlation of testosterone levels with the concentration of gonadotropins and prolactin has not been established. The increase in prolactin in the liquidators of the consequences of the Chernobyl accident, reliable in relation to the control group, remains for 12 years after the accident. 30–33 years after the accident, participants in the elimination of the consequences of the Chernobyl accident have significant age-related changes in hormonal indicators, among which the main is partial androgen deficiency.Conclusions. The persistent imbalance of hormones of the pituitary-gonadal endocrine axis at the time of 1994–1998 contributed to the clinical manifestation of circulatory diseases in liquidators – middle-aged men, clinical symptoms, on the other hand, aggravated diverse shifts in the functioning of this endocrine axis of regulation. In the later period of observation by 30–33 years after the accident, a decrease in androgen levels was accompanied by a steady increase in circulatory diseases in liquidators.