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Background: This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke. Methods: Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received lowfrequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated. Results: Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3, FT3 and TSH levels tended to increase at 4-week intervention and at the follow up (p < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (Fgroup = 5.319, p = 0.028); The cognitive scale at different time points in both groups showed an upward trend (p < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up (p < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores (r = 0.638, p < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change (r = 0.562, p < 0.05; r = 0.562, p < 0.05; r = 0.531, p < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function (r = 0.514, p < 0.05). Conclusion: Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function. [ABSTRACT FROM AUTHOR]

Radiofrequency electromagnetic fields (RF-EMFs) can penetrate tissues and potentially influence endocrine and brain development. Despite increased mobile phone use among children and adolescents, the long-term effects of RF-EMF exposure on brain and endocrine development remain unclear. This study investigated the effects of long-term evolution band (LTE) EMF exposure on thyroid hormone levels, crucial for metabolism, growth, and development. Four-week-old male mice (C57BL/6) were exposed to LTE EMF (whole-body average specific absorption rate [SAR] 4 W/kg) or a positive control (lead; Pb, 300 ppm in drinking water) for 4 weeks. Subsequently, the mice underwent behavioral tests including open field, marble burying, and nest building. Blood pituitary and thyroid hormone levels, and thyroid hormone-regulating genes within the hypothalamus–pituitary–thyroid (HPT) axis were analyzed. LTE exposure increased T3 levels, while Pb exposure elevated T3 and T4 and decreased ACTH levels. The LTE EMF group showed no gene expression alterations in the thyroid and pituitary glands, but hypothalamic Dio2 and Dio3 expressions were significantly reduced compared to that in the sham-exposed group. Pb exposure altered the hypothalamic mRNA levels of Oatp1c1 and Trh, pituitary mRNA of Trhr, and Tpo and Tg expression in the thyroid. In conclusion, LTE EMF exposure altered hypothalamic Dio2 and Dio3 expression, potentially impacting the HPT axis function. Further research is needed to explore RF-EMF's impacts on the endocrine system. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic–pituitary–thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels. Results: TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10−13, TWAS: P = 7.61 × 10−12 (whole blood), P = 6.40 × 10−13 (hypothalamus), P = 1.57 × 10−15 (pituitary), P = 4.27 × 10−15 (thyroid)), supported by colocalizations. Conclusion: Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.

Gonadotropin inhibitory hormone (GnIH) is essential for regulating the reproduction of mammals and inhibiting testicular activities in mice. This study aimed to explore the mechanism of GnIH on spermatogenesis and steroidogenesis by acting through the hypothalamus-pituitary-testis axis of mice. Mice were subcutaneously injected with different doses of GnIH (1 μg/150 μL, 3 μg/150 μL, 6 μg/150 μL, 150 μL saline, twice daily) for 11 days. Subsequently, luteinizing hormone (LH), testosterone (T), and inhibin B (INH B) levels of peripheral blood were determined, and the expression of GnRH synthesis-related genes (GnRH-1, Kiss-1, NPY) and gonadotropin synthesis-related genes (FSH β, LH β, GnRH receptor) in the hypothalamus and pituitary gland were respectively detected. Additionally, the expression of steroidogenesis-related genes/proteins (P450scc, StAR and 3β-HSD) and spermatogenesis-related proteins/genes including LH receptor (LHR), androgen receptor (AR), heat shock factor-2 (HSF-2) and INH B were analyzed using western blot and q-PCR. Results showed that GnIH treatment significantly reduced the concentration of LH in the peripheral blood. Further analysis revealed that GnIH treatment markedly reduced the expression of GnRHImRNA and Kiss-1 mRNA in the hypothalamus, and mRNA levels of FSH β, LH β, and GnRHR genes in the pituitary. We also observed that GnIH treatment significantly decreased T levels and expression of the P450scc, StAR, and 3β-HSD proteins in the testis. Furthermore, GnIH treatment down-regulated LHR, AR proteins, and HSF-2 gene in the testis. Importantly, the INH B concentration of and INH βb mRNA levels significantly declined following GnIH treatment. Additionally, GnIH treatment may induce germ cell apoptosis in the testis of mice. In conclusion, GnIH may suppress spermatogenesis and steroidogenesis by acting through the hypothalamus-pituitary-testis axis in mice. [ABSTRACT FROM AUTHOR]

Objective: The treatment of bipolar disorder (BD) remains challenging. The study evaluated the impact of the hypothalamic-pituitary-adrenal (HPA) axis/hypothalamic-pituitary-thyroid (HPT) axis and glucose metabolism on the clinical outcomes in patients with bipolar depression (BD-D) and manic bipolar (BD-M) disorders. Methods: The research design involved a longitudinal prospective study. A total of 500 BD patients aged between 18 and 65 years treated in 15 hospitals located in Western China were enrolled in the study. The Young Mania Rating Scale (YMRS) and Montgomery and Asberg Depression Rating Scale (MADRS) were used to assess the BD symptoms. An effective treatment response was defined as a reduction in the symptom score of more than 25% after 12 weeks of treatment. The score of symptoms was correlated with the homeostatic model assessment of insulin resistance (HOMA-IR) index, the HPA axis hormone levels (adrenocorticotropic hormone (ACTH) and cortisol), and the HPT axis hormone levels (thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4)). Results: In the BD-M group, the YMRS was positively correlated with baseline T4 (r = 0.349, p = 0.010) and fT4 (r = 0.335, p = 0.013) and negatively correlated with fasting insulin (r = -0.289, p = 0.013). The pre-treatment HOMA-IR was significantly correlated with adverse course (p = 0.045, OR = 0.728). In the BD-D group, the baseline MADRS was significantly positively correlated with baseline fT3 (r = 0.223, p = 0.032) and fT4 (r = 0.315, p = 0.002), while baseline T3 (p = 0.032, OR = 5.071) was significantly positively related to treatment response. Conclusion: The HPT axis and glucose metabolism were closely associated with clinical outcomes at 12 weeks in both BD-D and BD-M groups. If confirmed in further longitudinal studies, monitoring T3 in BD-D patients and HOMA-IR for BD-M could be used as potential treatment response biomarkers. [ABSTRACT FROM AUTHOR]

Oxidative stress, resulting from dysregulation in the secretion of adrenal hormones, represents a major concern in human health. The present review comprehensively examines various categories of endocrine dysregulation within the adrenal glands, encompassing glucocorticoids, mineralocorticoids, and androgens. Additionally, a comprehensive account of adrenal hormone disorders, including adrenal insufficiency, Cushing’s syndrome, and adrenal tumors, is presented, with particular emphasis on their intricate association with oxidative stress. The review also delves into an examination of various nutritional antioxidants, namely vitamin C, vitamin E, carotenoids, selenium, zinc, polyphenols, coenzyme Q10, and probiotics, and elucidates their role in mitigating the adverse effects of oxidative stress arising from imbalances in adrenal hormone levels. In conclusion, harnessing the power of nutritional antioxidants has the potential to help with oxidative stress caused by an imbalance in adrenal hormones. This could lead to new research and therapeutic interventions. [ABSTRACT FROM AUTHOR]

ABSTRACT: 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.

Oxidative stress, resulting from dysregulation in the secretion of adrenal hormones, represents a major concern in human health. The present review comprehensively examines various categories of endocrine dysregulation within the adrenal glands, encompassing glucocorticoids, mineralocorticoids, and androgens. Additionally, a comprehensive account of adrenal hormone disorders, including adrenal insufficiency, Cushing’s syndrome, and adrenal tumors, is presented, with particular emphasis on their intricate association with oxidative stress. The review also delves into an examination of various nutritional antioxidants, namely vitamin C, vitamin E, carotenoids, selenium, zinc, polyphenols, coenzyme Q10, and probiotics, and elucidates their role in mitigating the adverse effects of oxidative stress arising from imbalances in adrenal hormone levels. In conclusion, harnessing the power of nutritional antioxidants has the potential to help with oxidative stress caused by an imbalance in adrenal hormones. This could lead to new research and therapeutic interventions.

Progestins are mainly used in pharmacotherapy and animal husbandry and have received increasing attention as they are widely detected in various aquatic ecosystems. In this study, adult female western mosquitofish (Gambusia affinis) were exposed to different concentrations of norethindrone (NET) (solvent control, 5.0 (L), 50.0 (M), and 500.0 (H) ng/L) for 42 days. Behaviors, morphological parameters, histology of the thyroid, thyroid hormone levels (TSH, T3, and T4), and transcriptional levels of nine genes in the hypothalamic-pituitary-thyroid (HPT) axis were examined. The results showed that NET decreased sociality but increased the anxiety of G. affinis. Sociality makes fish tend to cluster, and anxiety may cause G. affinis to reduce exploration of new environments. Female fish showed hyperplasia, hypertrophy, and glial depletion in their thyroid follicular epithelial cells after NET treatment. The plasma levels of TSH and T4 were significantly reduced, but T3 concentrations were significantly increased in the fish from the H group. In addition, the transcripts of genes (tshb, tshr, tg, dio1, dio2, thrb) in the brains of fish in the M and H treatments were significantly stimulated, while those of trh and pax2a were suppressed. Our results suggest that NET may impact key social behaviors in G. affinis and interfere with the entire thyroid endocrine system, probably via affecting the transcriptional expression of upstream regulators in the HPT axis.

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual's ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition. [ABSTRACT FROM AUTHOR]

Many members of the American Thyroid Association played prominent roles in discovering the various aspects of the hypothalamic–pituitary–thyroid axis. This axis is fundamental for maintaining the normal serum levels of circulating thyroid hormones (THs) and thus the euthyroid state. The pituitary glycoprotein hormone, thyrotropin (TSH), controls the activity of the thyroid gland. Thyrotropin-releasing hormone and the negative feedback mechanism of circulating TH regulate the synthesis and the secretion of TSH. The dynamic interplay of these two dominant mechanisms has essential effects on TSH release. Therefore, the finding of abnormal serum levels of TSH often indicates the presence of a disorder of thyroid gland function. A summary of key historical discoveries in the understanding of the hypothalamic–pituitary axis is presented. [ABSTRACT FROM AUTHOR]

• OBS induced thyroid endocrine disruption effects in adult zebrafish and offspring. • OBS dysregulated transcription levels of key genes related to the HPT axis. • Thyroid hormone homeostasis in F1 offspring was altered after parental OBS exposure. • Parental OBS exposure significantly declined the swirl-escape rate of F1 offspring. • Developmental neurotoxicity might be associated with thyroid hormone dyshomeostasis. As an alternative to perfluorooctane sulfonate, sodium p -perfluorous nonenoxybenzene sulfonate (OBS) has been widely used and caused ubiquitous water pollution. However, its toxicity to aquatic organisms is still not well known. Therefore, in this study, parental zebrafish were exposed to OBS at environmentally relevant concentrations from ∼ 2 h post-fertilization to 21 days post-fertilization (dpf) in order to investigate the thyroid disrupting effects in F0 adults and F1 offspring. Histopathological changes, such as hyperplasia of thyroid follicular epithelia and colloidal depletion, were observed in F0 adults at 180 dpf. In F0 females, thyroxine (T4) levels were significantly reduced in 30 and 300 μg/L exposure groups, while triiodothyronine (T3) levels were significantly increased in 3 μg/L exposure group. For F0 males, significant increases of T4 and T3 levels were observed, revealing the sex-specific differences after the OBS exposure. The transcription levels of some key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were significantly disrupted, which induced the thyroid endocrine disruption effects in adult zebrafish even after a prolonged recovery period. For F1 offspring, the thyroid hormone (TH) homeostasis was also altered as T4 and T3 levels in embryos/larvae exhibited similar changes as F0 females. The transcription levels of some key genes related to the HPT axis were also significantly dysregulated, suggesting the transgenerational thyroid disrupting effects of OBS in F1 offspring. In addition, the decreased swirl-escape rate was observed in F1 larvae, which could be caused by disrupting gene expressions related to the central nervous system development and be associated with the TH dyshomeostasis. Therefore, parental OBS exposure at early life stage resulted in thyroid endocrine disruption effects in both F0 adult zebrafish and F1 offspring, and caused the developmental neurotoxicity in F1 larvae. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are industrial pollutants that act as endocrine disruptors and alter thyroid function. However, it is still unclear whether PCBs can affect hypothalamic thyrotropin releasing hormone (Trh) mRNA expression through TH signaling disruption. As salt-loading dehydration induces tertiary hypothyroidism in the hypothalamic parvocellular paraventricular nuclei (paPVN), and perinatal exposure to Aroclor 1254 (A1254) disrupts the hydric balance in rats, we hypothesized that TRH synthesis could be altered during dehydration in TRH neurons that control the hypothalamic–pituitary–thyroid (HPT) axis activity in rats perinatally exposed to A1254. We examined Trh mRNA expression in the paPVN and the response to salt-loading dehydration (hyperosmotic (hyper) stress) in the progeny of Wistar pregnant rats receiving 0 mg/kg BW (control) or 30 mg/kg BW A1254 daily from gestational days 10–19. Three-month-old offspring were subjected to normosmotic or hyper conditions and Trh mRNA, glucocorticoid receptor (GR) mRNA expression were measured in the PVN by RT-PCR. TRH mRNA and TRH+ neurons were measured in the paPVN by fluorescent in situ hybridization (FISH). As expected, Trh mRNA levels were decreased in the paPVN of male and female rats in the hyper group. Basal Trh mRNA expression and serum TSH were decreased in male rats in the A1254 group. Notably, Trh mRNA levels were further decreased in the paPVN of male and female A1254 + hyper rats, in which the GR mRNA expression was significantly decreased. These results support the hypothesis that perinatal exposure to A1254 results in inadequate adaptive response of the HPT axis in adulthood and contributes to dysregulation of the HPT axis response to salt-loading dehydration. [Display omitted] [ABSTRACT FROM AUTHOR]

Gas explosion (GE)-induced traumatic brain injury (TBI) can affect thyroid hormone (TH) homeostasis in miners. This study evaluated the effects of hepatic transthyretin and hypothalamic-pituitary-thyroid (HPT) axis on thyroids and explored the protective effect and mechanism of curcumin on GE-induced TBI. Thirty rats were randomly divided into three groups (10 per group): first group (control group)—rats received GE treatment once; second group (GE group)—rats received GE treatment (200 m from the source of the explosion once); third group (GE + Cur group)—rats received curcumin (Cur) by lavage at a dose of 100 mg/kg/day once every other day for 7 days after receiving GE. After GE, the pathological changes were analyzed by hemotoxylin and eosin staining, and the levels of serum reactive oxygen species (ROS), urine iodine (UI), THs, nuclear factor-kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and malondialdehyde (MDA) were analyzed using ELISA. Expression of proteins in the HPT axis of rats was examined by immunohistochemistry and Western blotting. We found that GE could induce pathologic changes in rat thyroid and liver. Serum levels of THs, NF-κB and serum redox state became unbalanced in rats after GE. GE could inhibit the biosynthesis and biotransformation of THs by affecting key HPT axis proteins. Additionally, GE reduced the level of hepatic transthyretin. Serum THs levels and thyroid sections were almost recovered to normal after curcumin treatment. The aforementioned key HPT axis proteins in the curcumin group showed opposite expression trends. In summary, GE affected THs balance while curcumin can protect against these injury effects by affecting TH biosynthesis, biotransformation, and transport, and inducing oxidative stress and inflammatory responses. [ABSTRACT FROM AUTHOR]

Background: This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke., Methods: Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received low-frequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated., Results: Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3,FT3 and TSH levels tended to increase at 4-week intervention and at the follow up ( p  < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (F group  = 5.319, p  = 0.028); The cognitive scale at different time points in both groups showed an upward trend ( p  < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up ( p  < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores ( r  = 0.638, p  < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change ( r  = 0.562, p  < 0.05; r  = 0.562, p  < 0.05; r  = 0.531, p  < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function ( r  = 0.514, p  < 0.05)., Conclusion: Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ma, Song, Tao, Xing and Zhang.)

Thyroid disorders are common in medicine, while bipolar disorders (BDs), though less frequent, are significant due to global prevalence, the economic burden on healthcare systems and long-term health implications, and the effects of psychiatric illness on quality of life. Clinical research has suggested thyroid hormone imbalances can cause psychiatric symptoms similar to the clinical features observed in BDs. Despite increased attention in this area of study, much remains unknown regarding how thyroid issues contribute to the development of BDs. This review explores the complex link between thyroid disorders and BDs, focusing on neurochemical dynamics, changes in the hypothalamic-pituitary-thyroid (HPT) axis, and genetic factors. Furthermore, this literature review examines the importance of understanding these factors in linking both conditions and emphasizes the necessity for therapies targeting their shared underlying mechanisms., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Norman et al.)

Propiconazole is used against fungal growth in agriculture and is released into the environment, but is a potential health threat to aquatic organisms. Propiconazole induces a generational effect on zebrafish, although the toxic mechanisms involved have not been described. The aim of this study was to investigate the potential mechanisms of abnormal offspring development after propiconazole exposure in zebrafish parents. Zebrafish were exposed to propiconazole at environmentally realistic concentrations (0.1, 5, and 250 μg/L) for 100 days and their offspring were grown in control solution for further study. Heart rate, hatching rate, and body length of hatched offspring were reduced. An increase in triiodothyronine (T3) content and the T3/T4 (tetraiodothyronine) ratio was observed, indicating disruption of thyroid hormones. Increased protein level of transthyretin (TTR) in vivo was consistent with the in silico molecular docking results and T4 competitive binding in vitro assay, suggests higher binding affinity between propiconazole and TTR, more than with T4. Increased expression of genes related to the hypothalamus-pituitary-thyroid (HPT) axis and altered metabolite levels may have affected offspring development. These findings emphasizes that propiconazole, even on indirect exposure, represents health and environmental risk that should not be ignored.

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.

Thyroid hormones (THs) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence TH synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programing of brain development, with implications for early identification of risk, primary prevention and intervention.

As perfluorooctanoic acid (PFOA) alternatives, hexafluoropropylene oxide dimeric acid (HFPO-DA) and hexafluoropropylene oxide trimeric acid (HFPO-TA) have been increasingly used and caused considerable water pollution. However, their toxicities to aquatic organisms are still not well known. Therefore, in this study, zebrafish embryos were exposed to PFOA (0, 1.5, 3 and 6 mg/L), HFPO-DA (0, 3, 6 and 12 mg/L) and HFPO-TA (0, 1, 2 and 4 mg/L) to comparatively investigate their thyroid disrupting effects and the developmental toxicity. Results demonstrated that waterborne exposure to PFOA and its two alternatives decreased T4 contents, the heart rate and swirl-escape rate of zebrafish embryos/larvae. The transcription levels of genes related to thyroid hormone regulation (crh), biosynthesis (tpo and tg), function (trα and trβ), transport (transthyretin, ttr), and metabolism (dio1 , dio2 and ugt1ab), were differently altered after the exposures, which induced the thyroid disrupting effects and decreased the heart rate. In addition, the transcription levels of some genes related to the nervous system development were also significantly affected, which was associated with the thyroid disrupting effects and consequently affected the locomotor activity of zebrafish. Therefore, HFPO-DA and HFPO-TA could not be safe alternatives to PFOA. Further studies to uncover the underlying mechanisms of these adverse effects are warranted. [Display omitted] • PFOA, HFPO-DA and HFPO-TA decreased T4 contents and the heart rate of zebrafish. • These PFASs caused thyroid disrupting effects in zebrafish. • These PFASs significantly altered expression of some genes related to the HPT axis. • These PFASs inhibited the swirl-escape rate of zebrafish larvae. • These PFASs also affected expression of genes related to the nervous development. [ABSTRACT FROM AUTHOR]

The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO 3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 μg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28–2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO 3 , PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease. [Display omitted] • First study on the thyroid disrupting effects of different coated AgNPs in zebrafish. • AgNO 3 was highly acute toxic, but AgNPs had stronger thyroid disrupting effects. • The toxicity of PVP-AgNPs may be caused by a combination of Ag+ and AgNPs. • The higher the Ag content in zebrafish, the stronger the thyroid disrupting effects. [ABSTRACT FROM AUTHOR]

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 (TR β), compromising the normal physiological function of TR β. 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. [Display omitted] • Penthiopyrad (PO) resulted in a significant reduction in larval swim bladder size and body weight. • PO perturbed the HPT axis, leading to marked rise in T4 and T3 levels in larvae. • PO and its metabolites may disrupt the binding of thyroid hormones to TR β. [ABSTRACT FROM AUTHOR]

Background: Thyrotropin-releasing hormone (TRH) was the first hypothalamic hormone isolated that stimulates pituitary thyrotropin (TSH) secretion. TRH was also later found to be a stimulator of pituitary prolactin and distributed throughout the brain, gastrointestinal tract, and pancreatic β cells. We previously reported the development of TRH null mice (conventional TRHKO), which exhibit characteristic tertiary hypothyroidism and impaired glucose tolerance due to insufficient insulin secretion. Although in the past five decades many investigators, us included, have attempted to determine the hypothalamic nucleus responsible for the hypothalamic–pituitary–thyroid (HPT) axis, it remained obscure because of the broad expression of TRH. Methods: To determine the hypothalamic region functionally responsible for the HPT axis, we established paraventricular nucleus (PVN)-specific TRH knockout (PVN-TRHKO) mice by mating Trh floxed mice and single-minded homolog 1 (Sim1)-Cre transgenic mice. We originally confirmed that most Sim1 was expressed in the PVN using Sim1-Cre/tdTomato mice. Results: These PVN-TRHKO mice exhibited tertiary hypothyroidism similar to conventional TRHKO mice; however, they did not show the impaired glucose tolerance observed in the latter, suggesting that TRH from non-PVN sources is essential for glucose regulation. In addition, a severe reduction in prolactin expression was observed in the pituitary of PVN-TRHKO mice compared with that in TRHKO mice. Conclusions: These findings are conclusive evidence that the PVN is the center of the HPT axis for regulation of serum levels of thyroid hormones and that the serum TSH levels are not decreased in tertiary hypothyroidism. We also noted that TRH from the PVN regulated prolactin, whereas TRH from non-PVN sources regulated glucose metabolism. [ABSTRACT FROM AUTHOR]

In addition to the hypophysiotropic thyrotropin‐releasing hormone (TRH)‐synthesizing neurons, a glial cell type, the tanycytes, also play a role in the regulation of the hypothalamic‐pituitary‐thyroid (HPT) axis. Tanycytes modulate the feedback regulation of the axis by regulating the local thyroid hormone availability in the median eminence where the hypophysiotropic axons terminate. Recently, we showed that tanycytes produce diacylglycerol lipase alpha (DAGLα), the synthesizing enzyme of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) that inhibits the release of TRH from the hypophysiotropic terminals in median eminence explants. To determine the importance of the endocannabinoid production of tanycytes, adult male Rax‐CreERT2//DAGLαfl/fl mice were treated with tamoxifen to induce a tanycyte specific decrease of DAGLα expression (T‐DAGLα KO). The effect of this genetic manipulation on the activity of the HPT axis was determined. Tanycyte specific decrease of DAGLα expression resulted in an approximately 2‐fold increase of TSHβ mRNA level that was accompanied by increased levels of circulating free T4. The TRH mRNA level was, however, not influenced by the genetic manipulation. In addition to the effects on the HPT axis, the T‐DAGLα KO mice showed increased fat mass ratio and decreased blood glucose levels. These data indicate that when endocannabinoid release of tanycytes is decreased, the disinhibition of the TRH release induces increased TSH synthesis and higher circulating T4 levels. Thus it suggests that in wild‐type mice, tanycytes exert a tonic inhibitory effect on the TRH release of hypophysiotropic axons. Furthermore, the endocannabinoid release of tanycytes also influences glucose homeostasis and fat deposition. [ABSTRACT FROM AUTHOR]

Abstract Understanding the relation between the environmental stress factors and the hypothalamus-pituitary-thyroid (HPT) axis efficiency can reduce the susceptibility to thyroid diseases. In our study, thyroid dysfunction was induced in female rats by administration of 40 mg Na F/kg.bd.wt/day for a month. Co-administration of the water extract of Arca noae (300 mg/kg. bw) was tested as a treatment for Na F induced thyroid dysfunction. A group of rats injected Arca noae extract only (300 mg/kg.bd.wt) was performed to observe the impact of the extract on the (HPT) axis in addition to the normal control group. Results showed that there was a significant decrease in serum triglycerides, total protein and albumin levels in the fluoride supplemented group in addition to abnormal levels of TSH, (T4) and (T3) compared to the control group. In the treated group there was an improvement in the proteins level and lipid profile but pseudo-corrected serum (T4) and (T3) levels were observed in addition to a continuous increase in TSH level. Histological findings confirmed the harmful effect of fluoride on both the non treated and the treated groups. Consequently, fluoride supplementation must be considered as a harmful stress that may affect permanently the HPT axis.

Abstract Background High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

Introduction: Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic-pituitary-thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels., Results: TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10-13, TWAS: P = 7.61 × 10-12 (whole blood), P = 6.40 × 10-13 (hypothalamus), P = 1.57 × 10-15 (pituitary), P = 4.27 × 10-15 (thyroid)), supported by colocalizations., Conclusion: Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances. [ABSTRACT FROM AUTHOR]

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances.

Selenium (Se), an essential component of deiodinases (DIOs), regulates the contents of thyroid hormones and thus improves animal growth. To explore the influences of selenium supplementation on fish growth metabolism, a total of 270 healthy grass carp (Ctenopharyngodon idella) were divided into three groups and feed three graded dietary selenium (0.141, 0.562, and 1.044 mg Se/kg) levels. The results showed that after 60-day feeding, dietary selenium improved the final body weight and specific growth rate (SGR) of grass carp. The hepatic DIO activities in selenium-supplemented groups were higher than those in control group. A significant increase in triiodothyronine (T3), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels was accompanied by a decrease in the contents of thyroxine (T4) and free thyroxine (FT4) in selenium-supplemented groups. The histopathological observation of thyroid suggested that selenium deficiency resulted in hypertrophy of follicular epithelial cells. Moreover, the gene relative expression levels of dio1, dio2, and dio3 showed an increasing trend with the rising concentration of dietary selenium. The transcription levels of HPT axis-related genes (crh, tsh-β, ttr, tr-s, tpo, nis) and GH/IGF1-related genes (gh, ghr, igf1, igf1r) were significantly upregulated in selenium-supplemented groups. No significant differences in the above indicators were observed between 0.562 and 1.044 mg Se/kg diet group except T3 content and dio1 relative expression ratio. These results indicate that dietary selenium supplementation improves the hepatic DIO activities and thyroid hormone metabolism and regulates the transcription levels of HPT and GH/IGF axis-related genes, which may be responsible for the growth promotion in grass carp. [ABSTRACT FROM AUTHOR]

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin‐like growth factor (GH/IGF) and hypothalamic–pituitary‐thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose‐depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF‐1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p <.05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p <.05), suggesting that ammonia exposure could perturb both GH/IGF‐axis and HPT‐axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3‐kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase‐polypeptide 1(s6k1) in the dorsal muscle were significantly down‐regulated in the fish exposed to ammonia (p <.05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dysregulation of the preovulatory surge (PS) leads to lowered egg production. The hypothalamo–pituitary–thyroid (HPT) axis has been shown to influence plasma progesterone levels and follicle ovulation. The presence of thyroid hormone receptors (THR) in the reproductive axis suggests possible effects of thyroid hormone. To further understand the potential role of thyroid hormone on the PS, HPT axis plasma hormone concentrations and gene expression were characterized surrounding the PS in average egg producing hens (AEPH), low egg producing hens (LEPH), and high egg producing hens (HEPH) (n = 3 hens/group). Data were analyzed using the mixed models procedure of SAS, with significance indicated at P < 0.05. Average egg producing hens and HEPH displayed lower levels of triiodothyronine (T3) and higher levels of thyroxine (T4) inside of the PS, whereas LEPH showed inverse T3 and T4 levels relative to the PS. Expression of mRNA for hypothalamic thyrotropin-releasing hormone (TRH), pituitary thyrotropin (TSHB), and the main thyroid hormone metabolism enzyme (DIO2) were downregulated during the PS in AEPH and HEPH. Low egg producing hens displayed higher expression of mRNA for hypothalamic TRH as well as pituitary TSHB and DIO2 compared with HEPH. Average egg producing hens expression of THR mRNAs was upregulated during the PS in the hypothalamus but downregulated in the pituitary. High egg producing hens showed decreased expression of THR mRNAs in both the hypothalamus and pituitary when compared with LEPH. In ovarian follicles, THR mRNAs were more prevalent in the thecal layer of the follicle wall compared with the granulosa layer, and expression tended to decrease with follicle maturity. Minimal differences in follicular THR expression were seen between LEPH and HEPH, indicating that THR expression is unlikely to be responsible for steroid hormone production differences occurring between LEPH and HEPH. Generally, downregulation of the HPT axis was seen during the PS in AEPH and HEPH, whereas upregulation of the HPT axis was seen in LEPH. Further studies will be required to clarify the role of the HPT axis in the regulation of ovulation and egg production rates in turkey hens.

Low and high egg producing hens exhibit gene expression differences related to ovarian steroidogenesis. High egg producing hens display increased expression of genes involved in progesterone and estradiol production, in the granulosa layer of the largest follicle (F1G) and small white follicles (SWF), respectively, whereas low egg producing hens display increased expression of genes related to progesterone and androgen production in the granulosa (F5G) and theca interna layer (F5I) of the fifth largest follicle, respectively. Transcriptome analysis was performed on F1G, F5G, F5I, and SWF samples from low and high egg producing hens to identify novel regulators of ovarian steroidogenesis. In total, 12,221 differentially expressed genes (DEGs) were identified between low and high egg producing hens across the four cell types examined. Pathway analysis implied differential regulation of the hypothalamo-pituitary-thyroid (HPT) axis, particularly thyroid hormone transporters and thyroid hormone receptors, and of estradiol signaling in low and high egg producing hens. The HPT axis showed up-regulation in high egg producing hens in less mature follicles but up-regulation in low egg producing hens in more mature follicles. Estradiol signaling exclusively exhibited up-regulation in high egg producing hens. Treatment of SWF cells from low and high egg producing hens with thyroid hormone in vitro decreased estradiol production in cells from high egg producing hens to the levels seen in cells from low egg producing hens, whereas thyroid hormone treatment did not impact estradiol production in cells from low egg producing hens. Transcriptome analysis of the major cell types involved in steroidogenesis inferred the involvement of the HPT axis and estradiol signaling in the regulation of differential steroid hormone production seen among hens with different egg production levels.

Low and high egg producing hens exhibit gene expression differences related to ovarian steroidogenesis. High egg producing hens display increased expression of genes involved in progesterone and estradiol production, in the granulosa layer of the largest follicle (F1G) and small white follicles (SWF), respectively, whereas low egg producing hens display increased expression of genes related to progesterone and androgen production in the granulosa (F5G) and theca interna layer (F5I) of the fifth largest follicle, respectively. Transcriptome analysis was performed on F1G, F5G, F5I, and SWF samples from low and high egg producing hens to identify novel regulators of ovarian steroidogenesis. In total, 12,221 differentially expressed genes (DEGs) were identified between low and high egg producing hens across the four cell types examined. Pathway analysis implied differential regulation of the hypothalamo-pituitary-thyroid (HPT) axis, particularly thyroid hormone transporters and thyroid hormone receptors, and of estradiol signaling in low and high egg producing hens. The HPT axis showed up-regulation in high egg producing hens in less mature follicles but up-regulation in low egg producing hens in more mature follicles. Estradiol signaling exclusively exhibited up-regulation in high egg producing hens. Treatment of SWF cells from low and high egg producing hens with thyroid hormone in vitro decreased estradiol production in cells from high egg producing hens to the levels seen in cells from low egg producing hens, whereas thyroid hormone treatment did not impact estradiol production in cells from low egg producing hens. Transcriptome analysis of the major cell types involved in steroidogenesis inferred the involvement of the HPT axis and estradiol signaling in the regulation of differential steroid hormone production seen among hens with different egg production levels. [ABSTRACT FROM AUTHOR]

Introduction: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops after exposure to traumatic and stressful life events. The hypothalamus is crucial in triggering hormonal responses to stress through the hypothalamic-pituitary-adrenal (HPA) axis. It is closely connected to the prefrontal cortex and limbic structures, particularly the amygdala and hippocampus, and acts as a central hub that combines various aspects of the stress response. Dysregulation of the stress system, including the HPA axis, has been implicated in the pathophysiology of PTSD. On the other hand, the hypothalamus also contributes to the development of PTSD through different pathways, such as the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes, as well as by secreting various hormones like growth hormone, prolactin, dopamine, oxytocin, and vasopressin. Methods and Materials: We conducted a thorough and methodical search for pertinent references using various databases, including Pubmed, Embase, MEDLINE, Scopus, Web of Science Core Collection, and Google Scholar. To ensure comprehensive coverage, we utilized different combinations of keywords such as "PTSD", "Hypothalamus", "HPA axis", "HPT axis", "HPG axis", "Growth hormone", "Oxytocin", "Prolactin", "Dopamine", "Vasopressin", "Rat model", "in vivo model" and "in vitro model", which were searched in the "title/abstract" field of these databases. The resulting articles were then carefully selected for their relevance to the topic at hand. Results: The findings of this review revealed that individuals with PTSD exhibit various abnormalities in the hypothalamic-pituitary-peripheral gland axes, including HPA, HPG, HPT, and posterior pituitary hormones such as oxytocin and vasopressin, as well as prolactin and growth hormone. These abnormalities may contribute significantly to the disease's development and symptoms' appearance. Conclusion: There is a close relationship between the hypothalamic endocrine function and PTSD. Gaining a more comprehensive understanding of the part that the hypothalamus plays in PTSD may lead to more effective treatments for this incapacitating disorder. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5), a ubiquitous environmental pollutant, has been indicated to affect thyroid hormone (TH) homeostasis in women, but the detailed mechanism behind this effect remains unclear. The objective of this study was to evaluate the roles of the hypothalamic-pituitary-thyroid (HPT) axis and hepatic transthyretin in the thyroid-disrupting effects of PM2.5. Sprague Dawley rats were treated with PM2.5 (0, 15 and 30 mg/kg) by passive pulmonary inhalation for 49 days; and recovery experimental group rats were dosed with PM2.5 (30 mg/kg) for 35 days, and no treatment was done during the subsequent 14 days. PM2.5 was handled twice a day by passive pulmonary inhalation throughout the study. After treatment, pathological changes were analyzed by performing haemotoxylin and eosin staining, measuring levels of THs and urine iodine (UI) in serum, plasma, and urine samples using enzyme-linked immunoabsorbent assay, and expression of proteins in the hypothalamus, pituitary, thyroid, and liver tissues of rats were analyzed by immunohistochemistry and Western blotting. The levels of oxidative stress factors, such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and nuclear factor-kappa B (NF-κB) in female rats’ plasma were also evaluated by ELISA. The results of these analyses revealed that PM2.5 treatment induced pathologic changes in rat thyroid and liver characterized by increased follicular cavity size and decreased amounts of follicular epithelial cells and fat vacuoles, respectively. Serum levels of triiodothyronine, thyroxine, and thyroid stimulating hormone were significantly decreased, plasma NF-κB level was increased and plasma redox state was unbalanced (enhanced ROS, MDA and Gpx levels; reduced SOD activities) in female rats treated with PM2.5 (P

Thyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells. [ABSTRACT FROM AUTHOR]

Objective: To explore the changes of HPA axis and HPT axis in rats with asthenozoospermia induced by cold stimulation, and its reproductive biology. Methods: Twenty-eight SPF-grade mature male SD rats were randomly divided into normal control group (N group, 12 rats) and cold stimulation group (C group, 16 rats). Before the end of modeling, the general conditions of rats including mental state, body weight, core body temperature and urine volume were recorded. After 23 weeks, the spermatozoa function was evaluated and the asthenozoospermia group (CA group) was established. At the same time, peripheral serum, HPA axis and HPT axis related tissues were collected. Then the levels of HPA axis and HPT axis related hormones of rats were detected by ELISA and radioimmunoassay. The morphological changes of HPA axis and HPT axis related tissue were observed under optical microscope. Results: Compared with N group, the response of rats in CA group was dull and the activity ability was decreased. The score of tail clamping test decreased significantly, while the core body temperature and urine volume increased significantly (P<0.05). The results of serum hormones showed that EPI and T3/T4 ratioin CA group were significantly higher than those in N group (P<0.05). Under optical microscope, the morphology of each tissue in group N was normal. Compared with group N, the hypothalamic paraventricular nucleus nerve cells in CA group proliferated and arranged in disorder; pituitary cell edema, blood sinus was not obvious, Hiirthle cell increased; adrenal edema was mainly in cortex and medulla; thyroid follicles atrophied and epithelial cells proliferated. Conclusion: The rats with asthenospermia induced by cold stimulation had the changes of HPA axis function and had the chronic stress. It is suggested that the function changes of HPA axis are participate in the occurrence and development of asthenospermia in this model. [ABSTRACT FROM AUTHOR]

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is inhibited by energy deficit, by acute or chronic stress, but activated by cold exposure or exercise. Because stress curtails acute cold induced activation of HPT, we evaluated the effect of chronic stress on HPT axis response to voluntary exercise, a persistent energy-demanding situation. Adult male and female Wistar rats were exposed to restraint stress, 30 min/day for 2 weeks, or to isolation (Iso) [post-natal day [PND] 30–63]. Exercise was performed (7 p.m.−7 a.m.) in a running wheel, sedentary controls stayed in individual cages (Sed); at 7 a.m. they were housed with their cage mate or individually (Iso); food intake by the exercised group was measured day and night to pair-fed Sed. At sacrifice, hormones, mRNA levels and tissue weights were quantified. Control or restrained adult rats had access to running wheel daily for 2 weeks. Compared to C, exercise decreased white adipose tissue (WAT) mass in females and males, increased hypothalamic paraventricular nucleus (PVN)-Trh expression in males proportionally to exercise performed, and increased TSH and T4 serum concentration in females. These changes were not detected in restrained groups. Starting at PND 63 control (2/cage) and isolated (1/cage) rats either exercised on 10 alternated nights or were sedentary. In control male animals, compared to Sed rats, exercise did not decrease WAT mass, nor changed HPT axis activity, but increased Pomc and deiodinase 2 (Dio2) expression in mediobasal hypothalamus (MBH), adrenergic receptor β3 and uncoupling protein-1 in brown adipose tissue. In control female animals, exercise decreased WAT mass, increased Pomc, Dio2, and Trhde expression in MBH, and TSH serum concentration. Iso females had lower TSH and T4 serum concentration, Dio2 and Trhde expression in MBH than controls. The stress response was higher in isolated males than females, but in males it did not alter the effects of exercise, in contrast to isolated females that had a blunted response to exercise compared to controls. In conclusion, chronic stress interferes with metabolic effects produced by exercise, such as loss of WAT mass, coincident with dampening of HPT activity.

Bullfrog ( Rana catesbeiana ) larvae inhabiting the main island of Japan overwinter as preclimax animals, whereas the larvae that reached climax in summer complete metamorphosis. We analyzed the mRNA expression levels of the adenohypophyseal hormones, hypothalamic hormones, and their receptors that are involved in controlling metamorphosis in tadpoles at various developmental stages available in summer and winter in order to understand the hormonal mechanism regulating metamorphosis progression. Corticotropin-releasing factor (CRF) and thyrotropin β-subunit (TSHβ) mRNA expression was enhanced as they reached the climax stage in metamorphosing summer tadpoles, although type 2 CRF receptor (CRFR2) mRNA levels demonstrated a tendency of elevation, indicating the activation of the hypothalamo-hypophyseal axis for stimulating the release of thyroid hormone in summer. Arginine vasotocin (AVT) mRNA levels were elevated as metamorphosis progressed, but mRNA expression levels were not synchronized with those of proopiomelanocortin (POMC) and V1b-type AVT receptor (V1bR). The elevation of mRNA levels of prolactin (PRL) 1A and type 3 thyrotropin-releasing hormone receptor (TRHR3), but not of thyrotropin-releasing hormone (TRH) precursor mRNA levels, was noted in climactic tadpoles, indicating that PRL mRNA levels are not simply dependent on the expression levels of TRH precursor mRNA. In the preclimactic larvae captured in winter, which are in metamorphic stasis, mRNA levels of pituitary hormones, hypothalamic factors, and their receptors remained low or at levels similar to those of the larvae captured in summer. These results indicate the relationship between the mRNA expression of metamorphosis-related factors and the seasonal progression/stasis of metamorphosis.

Objective: The treatment of bipolar disorder (BD) remains challenging. The study evaluated the impact of the hypothalamic-pituitary-adrenal (HPA) axis/hypothalamic-pituitary-thyroid (HPT) axis and glucose metabolism on the clinical outcomes in patients with bipolar depression (BD-D) and manic bipolar (BD-M) disorders., Methods: The research design involved a longitudinal prospective study. A total of 500 BD patients aged between 18 and 65 years treated in 15 hospitals located in Western China were enrolled in the study. The Young Mania Rating Scale (YMRS) and Montgomery and Asberg Depression Rating Scale (MADRS) were used to assess the BD symptoms. An effective treatment response was defined as a reduction in the symptom score of more than 25% after 12 weeks of treatment. The score of symptoms was correlated with the homeostatic model assessment of insulin resistance (HOMA-IR) index, the HPA axis hormone levels (adrenocorticotropic hormone (ACTH) and cortisol), and the HPT axis hormone levels (thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4))., Results: In the BD-M group, the YMRS was positively correlated with baseline T4 ( r = 0.349, p = 0.010) and fT4 ( r = 0.335, p = 0.013) and negatively correlated with fasting insulin ( r = -0.289, p = 0.013). The pre-treatment HOMA-IR was significantly correlated with adverse course ( p = 0.045, OR = 0.728). In the BD-D group, the baseline MADRS was significantly positively correlated with baseline fT3 ( r = 0.223, p = 0.032) and fT4 ( r = 0.315, p = 0.002), while baseline T3 ( p = 0.032, OR = 5.071) was significantly positively related to treatment response., Conclusion: The HPT axis and glucose metabolism were closely associated with clinical outcomes at 12 weeks in both BD-D and BD-M groups. If confirmed in further longitudinal studies, monitoring T3 in BD-D patients and HOMA-IR for BD-M could be used as potential treatment response biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhou, Chen, Zhao, Zhou and Sun.)

Purpose: To investigate the association of the hypothalamic-pituitary-testicular (HPT) axis with pro- and anti- oxidation, in relation to puberty and obesity in boys, before and after an aerobic exercise bout. Methods: This is a cross-sectional human observational study of 92 healthy normal-weight, obese pre- and early- pubertal boys that underwent a blood sampling, before, and after an aerobic exercise bout at 70% VO2max, until exhaustion. LH, FSH, total testosterone (tT) and markers of pro- (TBARS and PCs) and anti- (GSH, GSSG, GPX, catalase, TAC) oxidation were measured. Results: Baseline LH, FSH, and tT concentrations were greater in early, than in pre- pubertal boys, independently of weight status. Post-exercise, LH concentrations decreased in early pubertal boys while FSH concentrations did not change in any of the studied groups. Baseline and post-exercise tT concentrations were lower in obese than in normal-weight early pubertal boys, while baseline and post-exercise LH and FSH concentrations did not differ between these groups. Post-exercise tT concentrations increased in early pubertal obese boys. Baseline LH, FSH and tT concentrations correlated positively with baseline anti-oxidation markers concentrations in pre-pubertal boys. Baseline tT concentrations correlated positively with the increase of TAC concentrations in early pubertal normal-weight boys. In all boys, baseline LH concentrations were the best positive predictors for the exercise-associated increase of TAC concentrations. Conclusions: It appears that the HPT axis maturation during puberty (in particular its LH and testosterone components) is positively associated with the increase of anti-oxidation during a bout of aerobic exercise. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl phosphinic acids (PFPiAs, including 6:6, 6:8 and 8:8 PFPiAs) are one kind of emerging perfluoroalkyl substances and usually used as leveling and wetting agents in household cleaning products and pesticide formulations. In this study, zebrafish embryos (6 h post-fertilization [hpf]) were exposed to 6:6, 6:8 and 8:8 PFPiAs individually (0.5, 5 and 50 nM) for 168 hpf. 8:8 PFPiA at 5 and 50 nM reduced the body length, while all treatments of 6:8 and 8:8 PFPiA depressed the heartbeat of the zebrafish larvae. 8:8 PFPiA at 50 nM distinctly enhanced the thyroxine (T4) and triiodothyronine (T3) contents. In a negative feedback mechanism, the three PFPiAs remarkably suppressed the genes responsible for THs regulation (corticotropin-releasing hormone, crh ; thyroid stimulating hormone, tshβ), and 8:8 PFPiA displayed the strongest effect. In addition, 8:8 PFPiA significantly promoted the gene expressions corresponding to THs transport, metabolism and action (transthyretin, ttr ; uridine diphosphate glucuronosyltransferase, ugt1ab ; deiodinases, dio1 and dio2 ; thyroid hormone receptors, trα and trβ). As a result, 8:8 PFPiA displayed the strongest thyroid endocrine disrupting effect and significantly affected the growth of zebrafish larvae among the three PFPiAs in the present study. Unlabelled Image • 8:8 PFPiA inhibited the growth of zebrafish larvae. • 8:8 PFPiA significantly increased T4 and T3 contents and altered genes in the HPT axis. • Three PFPiAs suppressed genes regulating THs levels in negative feedback mechanism. • 8:8 PFPiA displayed the strongest thyroid endocrine disruption than 6:6 and 6:8 PFPiA. [ABSTRACT FROM AUTHOR]

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is inhibited by energy deficit, by acute or chronic stress, but activated by cold exposure or exercise. Because stress curtails acute cold induced activation of HPT, we evaluated the effect of chronic stress on HPT axis response to voluntary exercise, a persistent energy-demanding situation. Adult male and female Wistar rats were exposed to restraint stress, 30 min/day for 2 weeks, or to isolation (Iso) [post-natal day [PND] 30–63]. Exercise was performed (7 p.m.−7 a.m.) in a running wheel, sedentary controls stayed in individual cages (Sed); at 7 a.m. they were housed with their cage mate or individually (Iso); food intake by the exercised group was measured day and night to pair-fed Sed. At sacrifice, hormones, mRNA levels and tissue weights were quantified. Control or restrained adult rats had access to running wheel daily for 2 weeks. Compared to C, exercise decreased white adipose tissue (WAT) mass in females and males, increased hypothalamic paraventricular nucleus (PVN)- Trh expression in males proportionally to exercise performed, and increased TSH and T4 serum concentration in females. These changes were not detected in restrained groups. Starting at PND 63 control (2/cage) and isolated (1/cage) rats either exercised on 10 alternated nights or were sedentary. In control male animals, compared to Sed rats, exercise did not decrease WAT mass, nor changed HPT axis activity, but increased Pomc and deiodinase 2 (Dio2) expression in mediobasal hypothalamus (MBH), adrenergic receptor β3 and uncoupling protein-1 in brown adipose tissue. In control female animals, exercise decreased WAT mass, increased Pomc, Dio2 , and Trhde expression in MBH, and TSH serum concentration. Iso females had lower TSH and T4 serum concentration, Dio2 and Trhde expression in MBH than controls. The stress response was higher in isolated males than females, but in males it did not alter the effects of exercise, in contrast to isolated females that had a blunted response to exercise compared to controls. In conclusion, chronic stress interferes with metabolic effects produced by exercise, such as loss of WAT mass, coincident with dampening of HPT activity. [ABSTRACT FROM AUTHOR]