Hypothalamic-pituitary-thyroid Axis Research Articles

TSH-Receptor-Mediated regulation of thyroid hormones in the hypothalamic-pituitary thyroid axis

TSH-Receptor-Mediated regulation of thyroid hormones in the hypothalamic-pituitary thyroid axis

Intracerebroventricular prokineticin 2 infusion may play a role on the hypothalamus-pituitary-thyroid axis and energy metabolism

AimThe hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. Material and MethodsA total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1α and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. ResultsIcv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1α UCP1 in the WAT and BAT (p<0.05). ConclusionIcv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.

Thyroid status in patients with early stages of cancer of various localization

Purpose of the study. To determine the thyroid status of primary cancer patients in the early stages of uterine body cancer, kidney cancer, breast cancer, skin melanoma and lung cancer without a history of endocrine pathology.Patients and methods. The content levels of thyroid-stimulating hormone (TSH), thyroid hormones (THs) T4 and T3 of total and free forms were determined in the blood serum by RIA method in 132 patients with breast cancer, uterine body cancer, lung cancer, kidney cancer and skin melanoma (average age 55 years). The comparison group consisted of practically healthy donors.Results. Only in skin melanoma, serum TSH levels were reduced by 1.5 times (p &lt; 0.05). The T4 content was reduced by 1.4–1.7 times (p &lt; 0.05) in uterine body cancer and kidney cancer, increased in lung cancer patients and 16 % of breast cancer patients by 1.4–1.7 times though (p &lt; 0.05). A 1.3–1.5‑fold low (p &lt; 0.05) T3 level was found in breast cancer, kidney cancer, and skin melanoma, while an 1.6‑fold increase (p &lt; 0.05) was found in uterine body cancer. The revealed changes in THs by the type of clinical hyperthyroidism are an increase of 1.8 times (p &lt; 0.05) FT3 on the background of low TSH in the blood in patients with skin melanoma, and by the type of hyperthyroxinemia in patients with lung cancer and breast cancer, consisting in increased concentrations of T4 and FT3, and with free and total T3 levels in patients uterine body cancer, as well as FT4, without changes in TSH in the blood serum of patients, may be associated with the features of malignant pathology, since it is known that THs are proliferation stimulants and can build up in tumors.Conclusion. The development of a malignant tumor even in the early stages of the disease is perceived by the body as a threat for homeostasis and the response to the occurrence of neoplasm is the reaction of the hypothalamicpituitary-thyroid regulatory axis. As an outcome, patients develop euthyroid disorder syndrome.

Developmental toxicity and mechanism of dibutyl phthalate and alternative diisobutyl phthalate in the early life stages of zebrafish (Danio rerio)

Diisobutyl phthalate (DiBP), is widely chemical replacement for Dibutyl phthalate (DBP). Although DBP and DiBP have been detected in surface water worldwide, few studies to date have systematically assessed the risks of DBP and its alternatives to aquatic organisms. The present study compared DBP and DiBP for their individual and joint toxicity as well as thyroid hormone levels in zebrafish embryo. Transcripts of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were investigated in developing zebrafish larvae by application of real time polymerase chain reaction. The median half-lethal concentrations of DBP and DiBP to zebrafish at 96 h were 0.545 mg L−1 and 1.149 mg L−1, respectively. The joint toxic effect of DBP–DiBP (0.25–0.53 mg L−1) with the same ratio showed a synergistic effect. Thyroid hormones levels increased with exposure to 10 μg L−1 of DBP or 50 μg L−1 of DiBP, and exposure to both compounds significantly increased thyroid gland-specific transcription of thyroglobulin gene (tg), hyronine deiodinase (dio2), and transthyretin (ttr), indicating an adverse effect associated with the HPT axis. Molecular docking results indicated that DBP (−7.10 kcal/M and −7.53 kcal/M) and DiBP (−6.63 kcal/M and −7.42 kcal/M) had the same docking energy with thyroid hormone receptors. Our data facilities an understand of potential harmful effects of DBP and its alternative (DiBP).

Effects of penthiopyrad on the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish

Exposure to specific pesticides has been demonstrated to alter normal thyroid function of aquatic vertebrates. This study aimed to investigate the impact of penthiopyrad (PO) on the thyroid function of zebrafish, further elucidating its toxic mechanisms on the early developmental stages of zebrafish. Exposure to sublethal doses of PO (0.3–1.2 mg/L) for 8 days from 2 h after fertilization resulted in a significant reduction in larval swim bladder size and body weight, accompanied by developmental abnormalities such as pigment deposition and abnormal abdominal development. Perturbations in the hypothalamic-pituitary-thyroid (HPT) axis in larvae manifested as a marked upregulation of crh, tg, ttr, and ugt1ab expression, alongside downregulation of trβ expression, culminating in elevated thyroxine (T4) and triiodothyronine (T3) levels. Additionally, molecular docking results suggest that PO and its metabolites may disrupt the binding of thyroid hormones to thyroid hormone receptor beta (TRβ), compromising the normal physiological function of TRβ. These findings highlight the PO-induced adverse effects on the HPT axis of larvae under sublethal doses, eventually leading to abnormal development and growth inhibition.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. ObjectivesThis study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. MethodsThe study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. ResultsThe molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: −12.21, −0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: −18.33, −0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. ConclusionsIncreased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Patterns of Endocrine Disorders in a Neonatal Intensive Care Unit: A Single-Center Retrospective and Descriptive Study

Background: Endocrine disorders in infants in neonatal intensive care units (NICU) represent a significant clinical concern. Understanding the frequency and variety of these disorders is crucial for effective patient management. Objectives: This single-center retrospective study was conducted to examine the frequency and patterns of endocrine disorders among neonates in the NICU. Methods: We performed a retrospective review of 1 845 patient records over five years from the NICU at Çanakkale Onsekiz Mart University Health Practice and Research Hospital. The study included patients admitted between January 1, 2016, and March 31, 2021, who were diagnosed with endocrine disorders according to the international classification of diseases (ICD). Diagnostic criteria were used to identify and categorize endocrine disorders, primarily focusing on hypoglycemia, congenital hypothyroidism, hypothyroxinemia of prematurity, neonatal hyperthyrotropinemia (HTT), and disorders of calcium and magnesium metabolism. Data analysis was conducted using descriptive statistics. Results: Endocrine disorders were identified in 14.6% (CI: 13.15 - 16.38) of the neonates. The most prevalent were thyroid disorders (5.15%, CI: 4.23 - 6.25), disorders of calcium metabolism (3.68%, CI: 2.92 - 4.64), and disorders of glucose homeostasis (3.63%, CI: 2.87 - 4.58). Notably, neonatal HTT was more frequent than previously reported. The majority of endocrine issues occurred in premature infants. Hypoglycemia was the most frequent glucose homeostasis disorder, affecting 24.7% (CI: 19.9 - 30.2) of those diagnosed with endocrine issues. Among the cases with calcium metabolism disorders, hypocalcemia was predominant (79.4%, CI: 68.3 - 87.3), with the majority (89%, CI: 80.1 - 95.9) being classified as early neonatal hypocalcemia. Conclusions: Endocrine disorders, particularly those related to thyroid, calcium, and glucose homeostasis, remain prevalent issues in the NICU. Prematurity significantly contributes to these complications. The frequency and variety of endocrine disorders are likely to evolve with improvements in laboratory techniques and diagnostic methods. Future larger-scale studies could provide more comprehensive insights into these disorders.

Impact of methimazole-induced hypothyroidism on postnatal swine.

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.

Therapies to Treat Depression in Hypothyroid Patients

Abstract Hypothalamic–pituitary–thyroid axis seems to play an important role in the pathogenesis of depression in hypothyroid patients. Studies have shown that hypothyroidism can induce mood changes and major depressive disorders, but what governs the reason for this linkage and the most suitable therapy to manage this condition is not very clear. We aim to investigate the various existing therapies administered for depression due to hypothyroidism and the potential scope of yoga therapy to treat these conditions effectively. A systematic literature search of five databases, namely, EBSCO, SCOPUS, PROQUEST, PubMed, and Elsevier using the keywords in the area of “hypothyroidism, depression, and therapies” was carried out till the period 2023 following the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines to select the relevant English-language peer-reviewed articles for the study. The objective of this study was to present the work done so far in the field of treating depression in hypothyroidism through therapy techniques. The paper reviews 18 specific empirical studies on various available therapies administered for depression in hypothyroidism and based on the extant literature covers four broad themes: (1) hormone therapy, (2) antidepressant pharmacotherapy, (3) cognitive psychotherapy, and (4) yoga therapy. This review provides a clear need for more yoga therapy studies, as only two yoga studies were found for treating depression in hypothyroidism that have shown significant outcomes.

Effect of intermittent theta-burst stimulation on the thyroid and adrenal systems in resistant depressed patients

IntroductionDisturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently reported in treatment resistant depressed patients (TRDs). So far, the effects of intermittent theta-burst stimulation (iTBS) treatment—a form of repetitive transcranial magnetic stimulation (rTMS) technique—on the activity of the HPT and HPA axes are poorly understood.ObjectivesThe present study aimed to evaluate the effects of iTBS sessions, applied to the left dorsolateral prefrontal cortex, in TRDs with abnormal chronobiological HPT functioning at baseline (BL) possibly associated with hypercortisolemia.MethodsThe ∆∆TSH test (i.e., the difference between the thyrotropin response to protirelin tests [∆TSH] performed at 8 AM and 11 PM on the same day) and the dexamethasone suppression test (DST) were performed in 12 TRDs and 14 healthy hospitalized control subjects (HCs). To be enrolled in this study, patients had to show at BL reduced ∆∆TSH values (i.e., &lt; 2.5 mU/L) and a score of 18 or greater on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Post-DST cortisol maximum (CORmax) serum level in excess of 120 nmol/L defined DST non-suppression (i.e., hypercortisolemia)—6 TRDs were DST non-suppressors at BL. After 10 and 20 iTBS sessions the ∆∆TSH test and the DST were repeated in all inpatients. A positive clinical response was defined by a final HAMD-17 score ≤ 8.ResultsCompared to HCs, ∆∆TSH values were lower in TRDs at BL (p &lt; 0.00001), and remained reduced after 10 and 20 iTBS sessions (p &lt; 0.001 and p &lt; 0.02 respectively). Post-DST CORmax levels were higher in TRDs than in HCs at BL (p &lt; 0.01), but were comparable to those of HCs after 10 and 20 iTBS sessions. Responders (n = 5) were characterized by 1) a normalization of their ∆∆TSH values after 20 iTBS sessions (whereas after 10 iTBS sessions ∆∆TSH values were still reduced compared to HCs [p &lt; 0.05]), and 2) a normality of post-DST CORmax levels at BL—while after 10 and 20 iTBS sessions post-DST CORmax levels were decreased compared to HCs (p &lt; 0.006 and p &lt; 0.03 respectively). Non-responders (n = 7) showed 1) no significant change in their ∆∆TSH values which remained lower than those of HCs at each assessment (all p &lt; 0.001), 2) while increased post-DST CORmax levels found at BL (p &lt; 0.0008 vs. HCs) normalized from the 10th iTBS session.ConclusionsThe present pilot study suggests that successful iTBS treatment can restore the chronobiological activity of the HPT axis. Although iTBS may increase glucocorticoid receptor signaling, baseline hypercortisolemia could negatively impact subsequent response to iTBS treatment.Disclosure of InterestNone Declared

Association between multipollutant exposure and thyroid hormones in elderly people: A cross-sectional study in China

Environmental chemicals have been indicated to cause disruption of thyroid homeostasis in human populations. However, previous studies mostly focused on single group of chemicals. Herein, we investigate the independent and combined effects of multiple pollutants on thyroid homeostasis, including thyroid-stimulating hormone (TSH), total and free thyroxine (tT4 and fT4) and total and free triiodothyronine (tT3 and fT3) in elderly people. These environmental pollutants (n = 144) are from ten categories, including phenols, parabens, perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), synthetic pyrethroids (SPs), herbicides, and metals. Few studies have evaluated the health risks of these 144 chemicals, especially their joint effects. In single-pollutant evaluations, multiple linear regression (MLR) models were used to estimate the independent associations between multiple exposures and thyroid biomarkers. In multi-pollutant evaluations, elastic net regression and Bayesian kernel machine regression (BKMR) models were used to estimate the combined associations. The MLR models showed that 41 chemicals were significantly related to THs levels. BKMR models revealed the most important chemical groups: metals for TSH, PAHs, SPs and PCBs for tT4, herbicides and SPs for tT3. This study will contribute to the understanding of multipollutant exposure and help prioritize specific chemical groups related to thyroid hormone disruption.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry

Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. This research was not funded by any public, commercial, or not-for-profit agencies.

Changes in Lipid and Protein Peroxidation in Blood Serum and Respiratory Lungs Homogenate in Experimental Iodine Deficiency, Insulin Resistance and Their Combination

The relevance of the study is the prevalence of diet-induced metabolic disorders, in particular, iodine deficiency and insulin resistance. The aim of the study was to find out the features of lipids and proteins peroxidation in blood serum and lung tissue in rats with iodine deficiency, insulin resistance and their combination. Thyroid profile indicators, carbohydrate metabolism markers, proteins and lipids peroxidation were determined in animals kept on a standard diet (1st, control group), iodine-deficient diet (2nd group), under high-fructose feeding conditions (3rd group) and combination of iodine deprivation and the high-fructose diet (4th group). Indicators lipids and proteins free radical oxidation were determined in serum and homogenate of the pulmonary respiratory part. Iodine insufficient diet caused hypothyroid dysfunction, as evidenced by a decrease level of thyroid hormones and increase TSH in the blood serum of rats (2nd and 4th experimental groups). Increase in serum insulin and HOMA-IR index reflects the insulin resistance (3rd and 4th groups). Long-term iodine deprivation and a high-carbohydrate diet (three months) caused a violation of thyroid homeostasis and the development of insulin resistance, which are potentiated in their combination. Under such conditions oxidative stress develops, reflecting elevation of lipid and protein peroxidation products in blood serum (by 16,40-83,10 %, р&lt;0,05) and homogenate of the respiratory pulmonary section (by 39,61 % - 2,55 times, р&lt;0,05) according to the control. Increase the intensity of peroxidation in a combination of iodine-deficient and high-carbohydrate diets suggests a synergism of comorbid pathology and an increase in bronchopulmonary risks.

Distribution of Zinc in Muscle, Adipose Tissue and Blood Serum of Rats Under Conditions of Zinc-Deficient, Iodine-Deficient, High-Carbohydrate and High-Fat Diets

The relevance of the study is due to the prevalence of hypothyroid dysfunction, type II diabetes mellitus, and metabolic syndrome. The study was carried out on sexually mature male rats that were on a standard vivarium diet (control group), zinc-deficient, iodine-deficient, high-carbohydrate and high-fat diets. Under the experimental conditions, the distribution of zinc in blood serum, adipose (visceral fat) and muscle (femoral and tibial muscles) tissues was studied. The study showed a decrease in serum zinc content by 13.79-30.89 % (p&lt;0.05) compared to the control group, regardless of diet. The concentration of the trace element in adipose tissue was significantly reduced relative to the control under conditions of zinc deprivation (by 18.37 %, p&lt;0.05), and especially high-fat feeding (by 74.74 %, p&lt;0.001). The increase in the content of the trace element in muscles under conditions of zinc deficiency (by 36.84 %, p&lt;0.001) compared to the same indicator in animals fed a standard diet) is noteworthy. Taking into account the role of the bioelement in the maintenance of thyroid homeostasis, carbohydrate metabolism, and antioxidant potential, the detected changes involving zinc may act as a trigger for changes in the hormonal profile, metabolic and oxidative disorders.

Dynamics of Prolactin and Hormones of the Hypothalamic-Pituitary Thyroid Axis in Patients with Schizophrenia

Dynamics of Prolactin and Hormones of the Hypothalamic-Pituitary Thyroid Axis in Patients with Schizophrenia

ASSESSING THYROID FUNCTION: A REVIEW OF BIOCHEMICAL MARKERS AND TESTING STRATEGIES

The present work provides an in depth look at the biochemical markers and the testing strategies employed in appraising thyroid function. It involves the primary thyroid hormones such as TSH, T3, and T4 that are responsible for thyroid homeostasis and diagnosis of the dysfunction of the thyroid. The assessment also covers and evaluates the different testing methods and approaches to examine thyroid function which include immunoassays and mass spectrometry. The review offers the summary of advantages and disadvantages of different testing methods to increase the knowledge and to facilitate decision making regarding the diagnosis of thyroid function, and to improve the quality of care of thyroid-related conditions.

Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study

Disruption of thyroid homeostasis has been indicated in human studies on the effects of per- and polyfluoroalkyl substances (PFASs). However, limited research exists on this topic within the general Chinese population. Based on a substantial and representative sample of the Chinese adult population, our study provides insight into how PFASs specifically affect thyroid homeostasis. The study included 10 853 participants, aged 18 years and above, sampled from nationally representative data provided by the China National Human Biomonitoring (CNHBM). Weighted multiple linear regression and restricted cubic spline (RCS) models were used to explore the associations between eight individual PFAS concentrations and total thyroxine (T4), total triiodothyronine (T3), and the T4/T3 ratio. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (qgcomp) were employed to explore the joint and independent effects of PFASs on thyroid homeostasis. Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio. Perfluoroundecanoic acid (PFUnDA) [–0.07 (95 % confidence interval (CI): –0.08, –0.05)] exhibited the largest change in T3 level. PFUnDA also exhibited a higher weight compared to other PFAS compounds in qgcomp models. Additionally, a critical exposure threshold for each PFAS was identified based on nonlinear dose–response associations; beyond these thresholds, the decreases in T3 and T4 levels plateaued. Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups. These insights contribute to our understanding of how PFAS compounds impact thyroid health and emphasize the need for further research and environmental management measures to address these complexities.

Molecular mechanisms of hypothalamic-pituitary-ovarian/thyroid axis regulating age at first egg in geese

Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes in regulating poultry sexual maturity. Concurrently, there was evidence suggesting a potential co-regulatory relationship between these 2 axes. However, as of now, no comprehensive exploration of the key pathways and genes responsible for the crosstalk between the HPO and HPT axes in the regulation of AFE has been reported. In this study, we conducted a comparative analysis of morphological differences and performed transcriptomic analysis on the hypothalamus, pituitary, thyroid, and ovarian stroma between normal laying group (NG) and abnormal laying group (AG). Morphological results showed that the thyroid index difference (D-) value (thyroid index D-value=right thyroid index-left thyroid index) was significantly (P < 0.05) lower in the NG than in the AG, while the ovarian index was significantly (P < 0.01) higher in the NG than in the AG. Furthermore, between NG and AG, we identified 99, 415, 167, and 1182 differentially expressed genes (DEGs) in the hypothalamus, pituitary, thyroid, and ovarian stroma, respectively. Gene ontology (GO) analysis highlighted that DEGs from 4 tissues were predominantly enriched in the "biological processes" category. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that 16, 14, 3, and 26 KEGG pathways were significantly enriched (P < 0.05) in the hypothalamus, pituitary, thyroid, and ovarian stroma. The MAPK signaling pathway emerged as the sole enriched pathway across all 4 tissues. Employing an integrated analysis of the protein-protein interaction (PPI) network and correlation analysis, we found GREB1 emerged as a pivotal component within the HPO axis to regulate estrogen-related signaling in the HPT axis, meanwhile, the HPT axis influenced ovarian development by regulating thyroid hormone-related signaling mainly through OPN5. Then, 10 potential candidate genes were identified, namely IGF1, JUN, ERBB4, KDR, PGF, FGFR1, GREB1, OPN5, DIO3, and THRB. These findings establish a foundation for elucidating the physiological and genetic mechanisms by which the HPO and HPT axes co-regulate goose AFE.

GLP-1 Receptor Signaling Has Different Effects on the Perikarya and Axons of the Hypophysiotropic Thyrotropin-Releasing Hormone Synthesizing Neurons in Male Mice.

Background: Glucagon-like peptide 1 (GLP-1) is involved in the regulation of energy and glucose homeostasis. As GLP-1 has similar effects on the energy homeostasis as the hypophysiotropic thyrotropin-releasing hormone (TRH) neurons that regulate the hypothalamic-pituitary-thyroid (HPT) axis, we raised the possibility that the TRH neurons are involved in the mediation of the effects of GLP-1. Therefore, the relationship and interaction of the GLP-1 system and the TRH neurons of the hypothalamic paraventricular nucleus (PVN) were studied. Methods: To examine the anatomical and functional relationship of TRH neurons and the GLP-1 system in the PVN, immunocytochemistry, in situ hybridization, in vitro patch-clamp electrophysiology, metabolic phenotyping, and explant experiments were performed. Results: Our data demonstrate that the TRH neurons of the PVN are innervated by GLP-1 producing neurons and express the GLP-1 receptor (GLP-1R). However, not only do the GLP-1-innervated TRH neurons express GLP-1R but the receptor is also present in the axons of the hypophysiotropic TRH neurons in the blood-brain barrier free median eminence (ME) suggesting that peripherally derived GLP-1 may also influence the TRH neurons. In vitro, GLP-1 increased the firing rate of TRH neurons and depolarized them. In addition, GLP-1 directly stimulated the GABAergic input of a population of TRH neurons. Furthermore, GLP-1 inhibited the release of TRH from the hypophysiotropic axons in the ME. In vivo, peripheral GLP-1R agonist administration markedly inhibited the food intake and the energy expenditure, but had no effect on the TRH expression in the PVN and resulted in lower circulating free T4 levels. Conclusions: Our results indicate that GLP-1R activation has a direct stimulatory effect on TRH neurons in the PVN, but the activation of GLP-1R may also inhibit TRH neurons by facilitating their inhibitory inputs or by inhibiting the axon terminals of these cells in the ME. The innervation of TRH neurons by GLP-1 neurons suggests that TRH neurons might be influenced by both circulating GLP-1 and by GLP-1 neurons of the nucleus tractus solitarii. The lack of GLP-1R agonist-induced regulation of TRH neurons in vivo suggests that the HPT axis does not mediate the GLP-1R agonist-induced weight loss.

Thyroid function and thyroid homeostasis parameters are associated with increased urinary albumin excretion in euthyroid individuals over 60 years old from NHANES.

The relationship between thyroid function/homeostasis parameters and renal function has been extensively studied. However, the relationship between thyroid function and thyroid homeostasis parameters with albuminuria among elderly individuals remains unclear. The population was divided into an albuminuria group and a non-albuminuria group for baseline characteristic difference analysis. Multivariable logistic regression was used to test the association between thyroid function, and thyroid homeostasis parameters and albuminuria. The nonlinear relationship was explored with restricted cubic splines. Meanwhile, we investigated whether the relationship also existed in the diabetes and hypertension subgroups. Receiver operating characteristic (ROC) curves were used to assess the effectiveness of the indices. FT4 and TFQIFT4 were positively correlated with albuminuria (OR = 1.12; 95% CI = 1.02-1.23, p = 0.02; OR = 1.79; 95% CI = 1.08-2.99, p = 0.03), and FT3/FT4 was negatively correlated with albuminuria (OR = 0.03; 95% CI = 0.00-0.26, p = 0.003). Additionally, the nonlinear relationship between FT3/FT4 as well as TSHI and albuminuria was approximately U-shaped. Similar results were observed in the hypertension subgroup but not in the diabetes subgroup. There was a U-shaped nonlinear relationship between FT3 and albuminuria in the diabetes group. In addition, FT3/FT4 performed better than TFQI, TT4RI, and TSHI in ROC analyses for albuminuria prediction. FT4, TFQIFT4, and a low FT3/FT4 ratio were risk factors for albuminuria in euthyroid individuals over 60 years old. However, FT3 was more associated with albuminuria in the diabetes subgroup. TSH was not associated with albuminuria in any analysis. In our study, we attempted to provide more reasonable thyroid parameters and basis for evaluating patients with underlying albuminuria. FT3/FT4 may be used as a helpful indicator to predict albuminuria and provide novel ideas for the evaluation and treatment of albuminuria.