Thyrotropin-releasing Hormone Research Articles

Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae.

Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days. Chemical analysis demonstrated that FLX and its metabolic product (nonfluoxetine, NFLX) were accumulated in zebrafish larvae. The exposure resulted in decreased thyroid hormones (THs) levels, indicating thyroid endocrine disruption. Moreover, thyroid-stimulating hormone (TSH) content was significantly inhibited in a concentration-dependent manner after exposure to FLX. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (crh) and thyrotropin-releasing hormone (trh) were significantly up-regulated as a compensatory mechanism for the decreased TH contents accompanied with decreased tshβ mRNA expression. In addition, genes involved in thyroid hormone synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) and transport (transthyretin, ttr) were down-regulated after exposure to FLX in a concentration-dependent manner. The increased gene transcription of deiodinases (dio2) and uridinediphosphate-glucuronosyltransferase (ugt1ab) might be responsible for the decrease of TH contents. In addition, a significant inhibition in thyroid hormone receptors (trα and trβ) gene expression was observed upon treatment with FLX. All these results demonstrated that FLX could alter THs and TSH content as well as gene transcription in the HPT axis, exerting an endocrine disruption of the thyroid system in zebrafish larvae.

Low-molecular-weight Ligand of the Thyroid-stimulating Hormone Receptor with the Activity of a Partial Agonist and a Negative Allosteric Modulator.

Graves' disease is caused by overactivation of the thyroid-stimulating hormone receptor (TSHR). One approach for its treatment may be the use of negative allosteric modulators (NAM) of TSHR, which normalize TSHR activity and do not cause thyroid hormone (TH) deficiency. The aim of the work was to study the effect of a new compound 5-amino-4-(4-bromophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxylic acid N-tert-butylamide (TPY4) on the basal and TSH-stimulated TH production in cultured FRTL-5 thyrocytes and on basal and thyrotropin-releasing hormone (TRH)-stimulated TH levels in the blood of rats. TPY4 stimulated TH production by thyrocytes and increased TH levels when administered intraperitoneally and orally in rats. It also decreased the TSH-stimulated TH production in thyrocytes and the TRH-stimulated TH levels in rats. Thus, TPY4 is the first known allosteric regulator of TSHR, combining the properties of NAM and a partial agonist, and can be considered as a prototype of drugs for the treatment of Graves' disease.

A transient neurohormonal circuit controls hatching in fish.

Hatching is a critical event in the life history of oviparous species. The decision to hatch is often carefully timed to coincide with favorable conditions that will improve survival through early life stages. However, how the relevant cues are relayed to trigger hatching remains unknown. In this work, we show that thyrotropin-releasing hormone (Trh) is the neuroendocrine activator of hatching in zebrafish. To elicit hatching, Trh neurons form a transient circuit that deposits the peptide into the embryo's circulation. Trh also activates hatching in a distantly related fish species that separated more than 200 million years ago. Our results reveal an evolutionarily conserved neuroendocrine circuit that controls a major life event in oviparous fish species.

Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety.

Liraglutide and other glucagon-like peptide 1 receptor agonists (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. One potential mechanism is by activating neurons that inhibit the hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc). To identify these afferents, we developed a method combining rabies-based connectomics with single-nucleus transcriptomics. Here, we identify at least 21 afferent subtypes of AgRP neurons in the mouse mediobasal and paraventricular hypothalamus, which are predicted by our method. Among these are thyrotropin-releasing hormone (TRH)+ Arc (TRHArc) neurons, inhibitory neurons that express the Glp1r gene and are activated by the GLP-1RA liraglutide. Activating TRHArc neurons inhibits AgRP neurons and feeding, probably in an AgRP neuron-dependent manner. Silencing TRHArc neurons causes overeating and weight gain and attenuates liraglutide's effect on body weight. Our results demonstrate a widely applicable method for molecular connectomics, comprehensively identify local inputs to AgRP neurons and reveal a circuit through which GLP-1RAs suppress appetite.

Myeloperoxidase and Thyrotropin‐Releasing Hormone Within Leukaemia Stem Cells Increased Chemosensitivity in Acute Myeloid Leukaemia

ABSTRACTLeukaemia stem cells (LSCs) are major contributors to chemoresistance in acute myeloid leukaemia (AML). Identifying potential biomarkers within LSCs that can predict chemosensitivity in AML is key. This prospective study involved 20 consecutive de novo AML patients who underwent ‘7 + 3’ induction therapy. The patients were divided into CR (n = 15) and non‐CR (n = 5) groups. Using single‐cell RNA sequencing, we examined the cellular states of bone marrow mononuclear cells from AML patients at diagnosis and identified LSC among these cells. Our results showed that in non‐CR AML patients, a significant increase in the proportion of immature cells during haematopoiesis within the AML cell populations was observed. Moreover, the expression of myeloperoxidase (MPO) (log2 fold‐change = 0.89; adjusted p < 0.0001) and thyrotropin‐releasing hormone (TRH) (log2 fold‐change = 0.65; adjusted p < 0.0001) was higher within LSCs in the CR group than in the non‐CR group. Furthermore, patients with higher expression of MPO and TRH demonstrated improved relapse‐free survival (p = 0.002 for MPO; p = 0.009 for TRH) and overall survival (p = 0.002 for MPO; p < 0.001 for TRH). The connection between MPO or TRH and chemosensitivity could be linked with the downregulation of transforming growth factor and the upregulation of interferon‐α. In conclusion, MPO and TRH in LSCs could serve as chemosensitivity biomarkers in AML.

Pergolide mesylate administration does not decrease blood thyroid hormone concentrations and thyroid function in horses.

Pergolide, labeled for the treatment of pituitary pars intermedia dysfunction, is 90% protein bound and might cause a decrease in blood thyroid hormone concentrations by displacing them from binding proteins. This study investigated the effect of pergolide on the equine thyroid function. This was an analytic, observational, cohort study. Six horses (17 to 24 years old and 530 to 599 kg) received 1 mg of pergolide mesylate orally once a day from days 1 to 6. Total T4 (tT4) was measured daily from day 0 to 11 (before, during, and after pergolide treatment). Thyrotropin-releasing hormone (TRH) stimulation tests were conducted on days 0 and 6. Total T3 (tT3), tT4, and free T4 by equilibrium dialysis (fT4) were measured at baseline and 2 hours (tT3) and 4 hours (tT3, T4, and fT4) after TRH administration. The effect of pergolide on thyroid hormone concentration was determined by ANOVA, with P < .05 considered significant. No effect of pergolide was detected on tT4 during and after treatment. Administration of TRH resulted in significant increases in tT3 (effect size: +165.8 ng/dL [95% CI, 109.4 to 222.2 ng/dL]), tT4 (+1.162 µg/dL [95% CI, 0.7135 to 1.610 µg/dL]), and fT4 (+1.195 µg/dL [95% CI, 0.7195 to 1.670 µg/dL]). There was, however, no significant effect of pergolide on any thyroid hormone concentration. Pergolide has no detected effect on blood thyroid hormone concentrations and equine thyroid function. Protein-bound agents do not necessarily affect thyroid hormone concentrations. In horses with pituitary pars intermedia dysfunction, low thyroid hormone concentrations are likely due to the condition itself, not pergolide treatment.

Thyrotropin-Releasing Hormone Analog Taltirelin Inhibits Acute and Chronic Itch in Mice.

Itch is an unpleasant sensation that induces a desire to scratch. Chronic itch is accompanied by inflammatory skin diseases and causes repetitive scratching leading to tissue damage. The thyrotropin-releasing hormone analog taltirelin exerts analgesic effects on acute and chronic pain by activating the descending inhibitory systems. However, little is known regarding its effects on acute and chronic itch. In this study, we examined the effects of taltirelin on acute and chronic itch. Subcutaneous injection of chloroquine increased the number of scratching bouts in 30 min, whereas intraperitoneal injection of taltirelin reduced these episodes in a dose-dependent manner. In addition, chronic itch induced by diphenylcyclopropenone treatment was alleviated by taltirelin injection. These findings indicate that taltirelin alleviates acute and chronic itch in mice, and can be a potent therapeutic antipruritic drug.

Mass Spectrometry-Based Metabolomics Reveals a Salivary Signature for Low-Severity COVID-19.

Omics approaches were extensively applied during the coronavirus disease 2019 (COVID-19) pandemic to understand the disease, identify biomarkers with diagnostic and prognostic value, and discover new molecular targets for medications. COVID-19 continues to challenge the healthcare system as the virus mutates, becoming more transmissible or adept at evading the immune system, causing resurgent epidemic waves over the last few years. In this study, we used saliva from volunteers who were negative and positive for COVID-19 when Omicron and its variants became dominant. We applied a direct solid-phase extraction approach followed by non-target metabolomics analysis to identify potential salivary signatures of hospital-recruited volunteers to establish a model for COVID-19 screening. Our model, which aimed to differentiate COVID-19-positive individuals from controls in a hospital setting, was based on 39 compounds and achieved high sensitivity (85%/100%), specificity (82%/84%), and accuracy (84%/92%) in training and validation sets, respectively. The salivary diagnostic signatures were mainly composed of amino acids and lipids and were related to a heightened innate immune antiviral response and an attenuated inflammatory profile. The higher abundance of thyrotropin-releasing hormone in the COVID-19 positive group highlighted the endocrine imbalance in low-severity disease, as first reported here, underscoring the need for further studies in this area.

Application of composite reference intervals in the diagnosis of subclinical hypothyroidism in the elderly: a retrospective study.

Thyroid stimulating hormone releasing hormone (TSH) is a key indicator for diagnosing subclinical hypothyroidism (SCH). We evaluated factors affecting TSH levels in elderly SCH, establishing a composite reference interval, and comparing it with traditional one in diagnosis. We collected data on patients aged ≥60 undergoing physical examinations in Chengdu, screening the influencing factors associated with TSH. Then, a two-dimensional composite reference interval was established for TSH and FT4, and the differences between the new and traditional diagnosing methods were compared. The incidence of subclinical thyroid dysfunction was about 14%, with SCH accounting for 97%. Regression analysis found that TSH levels increase as FT4 and uric acid levels decrease. Compared with the two-dimensional composite reference interval, the traditional one has a higher incidence rate of SCH. Compared with the two-dimensional composite reference interval, the traditional one is more likely to overestimate the incidence rate of SCH, leading to excessive diagnosis and treatment.

Seasonal changes in activity of hypothalamic thyroid hormone system in different winter phenotypes of Djungarian hamster (Phodopus sungorus).

Although the Djungarian hamster (Phodopus sungorus) is a seasonality model, it presents substantial variability in winter acclimation. In response to short photoperiod, some individuals express a suite of winter traits such as low body mass, regressed gonads, white fur, and daily torpor, while others develop only some adjustments or maintain a summer phenotype. Despite comprehensive research, the mechanisms underlying polymorphism of winter phenotype are still unknown. We compared key elements of the hypothalamic thyroid hormone system, as well as the tanycyte architecture in hamsters of both sexes. Individuals presented different responses to short photoperiod characterized either as phenotypes (non-responder, partial-responder and full-responder) or photoresponsive index. We measured the expression of genes coding iodothyronine deiodinase 2 and 3, monocarboxylate transporter 8, thyrotropin-releasing hormone, and somatostatin in 40 individuals and counted the number of immunolabeled tanycyte processes in standardized regions of interest around the third ventricle in 30 individuals. Animals acclimated to short photoperiod presented a downregulation of diodinase 2 and somatostatin and an upregulation of deiodinase 3, as well as a decreased number of tanycyte processes, compared to long photoperiod-exposed individuals. Although phenotypes did not differ in gene expression, the higher the photoresponsive index, the lower was the deiodinase 2 expression and the higher the deiodinase 3 expression. Partial-responders and full-responders had less tanycyte processes than non-responders, and the number of tanycyte processes correlated with the photoresponsive index. Sexes differed neither in their seasonal response, nor hypothalamic gene expression, but females had more tanycyte processes. Our results are in accordance with studies emphasizing the pivotal role of thyroid hormones in seasonal response. We suggest that the whole spectrum of winter phenotypes exists within the population of Djungarian hamsters and that it is reflected also at the level of neuroendocrine regulation. However, the neuroendocrine underpinnings of winter phenotype polymorphism require further investigation.

7170 Plasticity of the Hypothalamic Tuberoinfundibular Dopaminergic Neuronal Network in Lactating Rats

Abstract Disclosure: P. Papaioannou: None. T. Georgescu: None. D.R. Grattan: None. S. Bunn: None. S. Yip: None. The tuberoinfundibular dopaminergic (TIDA) neurons play a crucial role in regulating prolactin secretion. Their synchronized network activity with slow but highly rhythmic firing pattern is important for dopamine release in rats[1]. While this unique TIDA network activity is vital for prolactin negative feedback in non-lactating conditions, its behaviour during lactation, when prolactin demand is high, remains unknown. Our hypothesis posited that the TIDA neuronal network in lactating rats becomes desynchronized, disrupting the negative feedback loop. To test this, we utilized ex-vivo Ca2+ imaging to simultaneously monitor population-wide TIDA neuron activity in non-lactating (NL; n=13) and lactating (L; n=10) rats injected with a cre-inducible adeno-associated virus (AAV) containing the Ca2+ indicator, GCaMP6s, into their arcuate nucleus. Analysis of neuronal network synchronicity revealed significant desynchronization in the TIDA network during lactation, as indicated by a markedly lower mean correlation coefficient matrix (CM) compared to non-lactating conditions (NL: 0.87±0.02, n= 26 sections vs L: 0.22±0.03, n=29 sections; p&amp;lt;0.001, Student’s t-test). Furthermore, the oscillatory activity patterns of these desynchronized TIDA neurons displayed a significantly lower cell rhythmicity index (RI) in lactating animals compared to non-lactating ones (NL: 0.17±0.01, n=186 cells vs L: 0.70±0.02, n=77 cells; p&amp;lt;0.001, Student’s t-test). Interestingly, within these low rhythmic neurons, some exhibited higher while others showed lower firing frequencies compared to non-lactating TIDA neurons. After 7 days post-weaning (n=4 animals), the TIDA network activity returned to non-lactating behaviour (CM = 0.85 ± 0.04, n=6 sections and RI = 0.17±0.01; n=47 cells). In summary, our findings demonstrate a reversible reconfiguration of the TIDA neuronal networks during lactation, characterized by low rhythmic oscillations and individual unique firing patterns, leading to diminished intercellular synchrony that may impede dopamine release, ultimately facilitating prolactin release to support lactation. Once weaned, the TIDA neuronal network reset to NL state to allow a new reproductive cycle. [1] Lyons, D. J., Horjales-Araujo, E. &amp; Broberger, C. Synchronized network oscillations in rat tuberoinfundibular dopamine neurons: switch to tonic discharge by thyrotropin-releasing hormone. Neuron 65, 217-229, doi:10.1016/j.neuron.2009.12.024 (2010). Presentation: 6/2/2024

Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3

Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1+/Onecut1/2+ proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH)+ glutamate neurons through neuron navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice reduced NAV2 mRNA, as well as neurite complexity in Onecut3-containing neurons, while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring, and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal subtypes and many species, underpins the polarization and morphological plasticity of phenotypically distinct neurons that descend from a common pool of Ascl1+ progenitors in the hypothalamus.

8759 Mild Iodine Deficiency During Pregnancy Impairs Hypothalamus-Pituitary-Thyroid Function Programing of the Adult Male Offspring

Abstract Disclosure: M. Oliveira: None. E. Tavares: None. G. Henrique: None. J. Pinto: None. C. Serrano-Nascimento: None. Introduction: Iodine plays a crucial role in the biosynthesis of thyroid hormones and is essential for proper thyroid embryonic development. While severe iodine deficiency during pregnancy and lactation has well-documented deleterious effects, the consequences of mild iodine deficiency (MID) remain not fully understood. MID during pregnancy is a reality in numerous countries, even in regions with seemingly adequate iodine supply in the diet. Previous studies have highlighted the adverse impact of MID on neurological development in offspring, but comprehensive data on thyroid function, particularly in progeny at different developmental stages, are lacking. This study aimed to investigate the repercussions of MID during pregnancy on the programming of thyroid dysfunctions during adulthood. Methods: Female CD1 mice were subjected to iodine-deficient animal chow and iodine-supplemented water, either at normal (NI; 0.2 mg/L) or mild iodine deficiency (MID; 0.8 mg/L) levels during pregnancy. Gene and protein expression in the hypothalamus, pituitary, and thyroid of adult male offspring animals (PND90) were evaluated using qPCR and Western blotting. Additionally, this study explored MID-induced programming of offspring thyroid gene expression through epigenetic mechanisms. Results: Maternal MID exposure led to increased gene and protein expression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) in the hypothalamus and pituitary of the offspring animals. Thyroid protein and gene expression of sodium iodide symporter (NIS), TSH receptor (TSHR), thyroid peroxidase (TPO), thyroglobulin (TG), paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and monocarboxylate transporter 8 (MCT8) were elevated in the offspring of MID-exposed animals. Epigenetic mechanisms appeared to contribute to the augmented thyroid gene expression in MID-exposed animals, with decreased DNA methyltransferase expression and reduced thyroid DNA global methylation. Additionally, histone 3 hypomethylation and increased acetylation of histones 3 and 4 were observed. Conclusion: The study suggests that MID exposure during pregnancy can be as harmful as severe iodine deficiency in programming the hypothalamus-pituitary-thyroid (HPT) axis, leading to HPT dysfunction during adult life. Consequently, our data suggest that monitoring iodine intake throughout pregnancy is crucial to prevent the occurrence of thyroid disorders in offspring during adulthood. Presentation: 6/1/2024

Thyroid Endocrine Disruption and Mechanism of the Marine Antifouling Pollutant 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one.

The antifoulant 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) is an emerging pollutant in the marine environment, which may disrupt the thyroid endocrine system. However, DCOIT toxicity in relation to thyroid endocrine disruption and the underlying mechanisms remains largely unclear. In this study, in vivo, in silico, in vitro, and ex vivo assays were performed to clarify DCOIT's thyroid toxicity. First, marine medaka (Oryzias melastigma) were exposed to environmentally realistic concentrations of DCOIT for an entire life cycle. The results demonstrated that DCOIT exposure potently stimulated the hypothalamic-pituitary-thyroid axis, characterized by hyperthyroidism symptom induction and prevalent key gene and protein upregulation in the brain. Moreover, the in silico and in vitro results evidenced that DCOIT could bind to thyroid hormone receptor β (TRβ) and interact synergistically with triiodothyronine, thus promoting GH3 cell proliferation. The CUT&Tag experiment found that DCOIT interfered with the affinity fingerprint of TRβ to target genes implicated in thyroid hormone signaling cascade regulation. Furthermore, ex vivo, Chem-seq revealed that DCOIT directly bound to the genomic sequences of thyrotropin-releasing hormone receptor b and thyroid-stimulating hormone receptor in marine medaka brain tissues. In conclusion, the current multifaceted evidence confirmed that DCOIT has a strong potency for thyroid endocrine system disruption and provided comprehensive insights into its toxicity mechanisms.

Gene expression in the hypothalamic-pituitary-thyroid axis in Seriola rivoliana early larvae development at different temperatures

We analyzed the expression of genes involved in the hypothalamic-pituitary-thyroid axis (HPT-axis) in the longfin yellowtail Seriola rivoliana early larva, including temperature effects (22, 26 and 28 °C) and days of development (day one, day two, and day six after hatching). We aimed to determine if egg and larval incubation at different temperatures could disrupt this critical endocrine axis, which, in an aquaculture context, it could provoke mortality during early metamorphosis. There was a significant interaction between temperature and developmental timing on the relative expression of thyrotropin releasing hormone (trh). Larvae at 22 °C was the longest and increased more trh expression than larvae at higher temperatures. Interestingly, thyrotropin stimulating hormone (tsh) was highly expressed after hatching. Subsequently, it was downregulated at any temperature at least until day four, suggesting a temporal inhibition of the HPT axis. Therefore, we suggest that tsh-binding (tshr) to follicles should have occurred from hatching, creating a further “cascade effect” of upregulation of larval thyroglobulin (tg) from day two in a temperature-dependent manner. Consequently, new thyroid hormones should have been produced after yolk sac absorption. The above may indicate a narrow window of larval survival, where the larval transition from endogenous to exogenous feeding would depend on the correct timing to synthesize tg. Temperature significantly affected the expressions of deiodinase 1 (dio1-downregulated) and deiodinase 2 (dio2-upregulated) after hatching. The expressions of thyroid receptors alpha (trα) and beta (trβ) remained constant after hatching without significant effects of temperature and days of development. Then, the differential expression on day six showed that all HPT-axis transcripts increased their expressions as larvae developed, which suggested a functional HPT. Finally, there was no evidence that any temperature would disrupt the endocrine’s larval axis, which indicated that the longfin yellowtail has a wide temperature adaption. Nevertheless, based on tg upregulation, we suggest that larvae should be maintained around 25–26 °C after hatching for a better chance of survival and development.

Roger Guillemin: A Century of Life, A Legacy of Endocrine Discoveries.

Dr. Roger Guillemin was a French physiologist who won the Nobel Prize in 1977. His pioneering research and fierce competition led to the isolation and identification of hypothalamic hormones, including thyrotropin-releasing factor (TRF), luteinizing hormone-releasing factor (LRF), and somatostatin. These discoveries transformed the knowledge of the role of the hypothalamus in endocrine control. His work not only helped in the advancement of scientific understanding but also directed the field for decades. His research continues to resonate today, shaping modern endocrinology and impacting the global treatment of endocrine disorders.

Age-Related Features of the Function of the Hypothalamic-Pituitary-Thyroid (HPT) Axis in Nonhuman Primates under Constant Lighting.

We studied the features of the functioning of the hypothalamic-pituitary-thyroid (HPT) axis under conditions of constant (4 weeks) lighting (LED lamps intended for office and residential premise) on a translational model of young adult and old female rhesus monkeys, in particular taking into account their behavior. Constant lightning had no significant effect on the levels of thyroid-stimulating hormone, thyroxine, and triiodothyronine under basal conditions in all animals, regardless of age and behavioral characteristics, but induced a decrease in thyroid function under conditions of its activation with thyrotropin-releasing hormone, mainly in old animals.

Eje hipotálamo-hipofisario. Regulación neurohormonal, implicaciones patológicas, pruebas funcionales hipofisarias, indicaciones e interpretación

The hypothalamic-pituitary axis is a crucial system for maintaining homeostasis by integrating hormonal and neuronal inputs and outputs. Almost all bodily functions are regulated directly or indirectly by this axis. The hypothalamus, a small but vital brain region, monitors various inputs and maintains physiological set points through hormonal secretion, coordinating with the pituitary gland. This regulation involves multiple feedback mechanisms and interactions with other brain areas.The hypothalamus is anatomically divided into several regions and nuclei, each with specific functions. It produces a variety of hormones, including growth hormone-releasing hormone, corticotropin-releasing hormone, thyrotropin-releasing hormone, and gonadotropin-releasing hormone. These hormones regulate the secretion of corresponding hormones from the anterior pituitary gland, which control several physiological processes, including growth, metabolism, reproduction, and stress response.Pathological implications of hypothalamic-pituitary axis dysfunctions include endocrine disorders such as hyperprolactinemia, growth hormone deficiency, and hypogonadism. In addition, hypothalamic damage can lead to neurological and behavioral problems such as sleep disturbances and thermoregulation.

Perinatal exposure to Aroclor 1254 disrupts thyrotropin-releasing hormone mRNA expression in the paraventricular nucleus of male and female rats

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.

The influence of extended fasting on thyroid hormone: local and differentiated regulatory mechanisms.

The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body's energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.