Thyrotropin-releasing Hormone Research Articles

Receptor modulators associated with the hypothalamus -pituitary-thyroid axis.

The hypothalamus-pituitary-thyroid (HPT) axis maintains normal metabolic balance and homeostasis in the human body through positive and negative feedback regulation. Its main regulatory mode is the secretion of thyrotropin (TSH), thyroid hormones (TH), and thyrotropin-releasing hormone (TRH). By binding to their corresponding receptors, they are involved in the development and progression of several systemic diseases, including digestive, cardiovascular, and central nervous system diseases. The HPT axis-related receptors include thyrotropin receptor (TSHR), thyroid hormone receptor (TR), and thyrotropin-releasing hormone receptor (TRHR). Recently, research on regulators has become popular in the field of biology. Several HPT axis-related receptor modulators have been used for clinical treatment. This study reviews the developments and recent findings on HPT axis-related receptor modulators. This will provide a theoretical basis for the development and utilisation of new modulators of the HPT axis receptors.

The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies

BackgroundThis study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabolites on thyroid hormones based on population data and in vitro experiments. Methods312 adults participated in this study. Urinary DEHP metabolites were determined by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). Two pharmacokinetic models were used to evaluate the estimated daily intake (EDI) and hazard quotient (HQ) of the adults. Multiple linear regression and mediating effect models were used to evaluate the target associations. In cell experiments, thyroid follicular epithelial (Nthy-ori3–1) cells were exposed to mono (2-ethylhexyl) phthalate (MEHP) for testing. The inhibitions of ERα and Notch pathway were conducted by siRNA and Notch pathway inhibitor DAPT. ResultsThe detection rate of five DEHP metabolites was 97.1∼100.0%. The HQ value of 0.3% of adults was higher than 1. The levels of urinary DEHP metabolites were significantly correlated with thyrotropin (TSH), thyrotropin-releasing hormone (TRH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) and gene (estrogen receptor α (ERα), Notch1, Dll4) levels. The ERα-Notch pathway played a mediating role in the association between DEHP metabolite levels and FT4. The cell results showed, the levels of FT3 and FT4 in cell supernatant decreased after MEHP exposure, and the downward trend was reversed after ERα and notch pathways were inhibited, notch pathway genes also decreased after ERα inhibition. ConclusionAdults in the Jilin Province of China were widely exposed to DEHP. ERs-Notch pathway played an important role in the effect of DEHP metabolites on thyroid hormones.

Determining the impact of rovatirelin which is a thyrotropin-releasing hormone in the treatment of ataxias in spinocerebellar degenerations

Determining the impact of rovatirelin which is a thyrotropin-releasing hormone in the treatment of ataxias in spinocerebellar degenerations

Influence of feeding and other factors on adrenocorticotropin concentration and thyrotropin-releasing hormone stimulation test in horses and ponies.

The basal (bACTH) and post-thyrotropin-releasing hormone stimulation concentration of adrenocorticotropin (pACTH) are recommended for diagnosis of pituitary pars intermedia dysfunction (PPID). Many factors influence bACTH (e.g., disease, age, month) and some affect the results only in autumn (e.g., breed, colour, sex). There are discrepancies about the impact of feeding on b/pACTH. To determine whether feeding, month, age, breed, colour, sex and body condition score affect b/pACTH. Prospective crossover. Sixty-one animals were divided into groups: healthy, PPID, treated-PPID. The b/pACTH was measured three times (1 mg protirelin; blood collection after 10 min; mid-November to mid-July) after different feedings: fasting, hay, hay + grain. Friedman's test was applied to evaluate the influence of feeding on b/pACTH and linear mixed model to evaluate impact of further factors. The b/pACTH was not significantly affected by feeding (p = 0.7/0.5). The bACTH was lowest in healthy (29.3 pg/mL, CI 9-49.5 pg/mL) and highest in PPID-group (58.9 pg/mL, CI 39.7-78.1 pg/mL). The pACTH was significantly lower in healthy (396.7 pg/mL, CI 283.2-510.1 pg/mL) compared to PPID (588.4 pg/mL, CI 480.7-696.2 pg/mL) and treated-PPID group (683.1 pg/mL, CI 585.9-780.4 pg/mL), highest in July (881.2 pg/mL, CI 626.3-1136.3 pg/mL) and higher in grey (723.5 pg/mL, CI 577.5-869.4 pg/mL) than other colours (338.7 pg/mL, CI 324.8-452.5 pg/mL). The size of effect for those variables was >0.5. Small number of animals, subsequent bACTH measurements were significantly lower in each horse. There was no evidence that feeding influences the b/pACTH. There was evidence that pergolide affects the bACTH but it had little effect on pACTH. Further investigation of the impact of month and coat colour on b/pACTH is warranted to better interpret the results.

Total thyroxine and thyroid-stimulating hormone responses of healthy cats to different doses of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) stimulation can be used as a test of thyroid function and pituitary thyrotropin (thyroid-stimulating hormone, TSH) reserve, but optimal stimulation testing protocols in cats are unreported. We randomly divided 6 healthy young adult cats into 3 groups of 2 and administered 3 different intravenous doses of TRH (0.01, 0.05, 0.1 mg/kg) at weekly intervals in our crossover study. Serum TSH and thyroxine (T4) concentrations were measured using chemiluminescent immunoassay before, and at 30 and 60 min after, TRH administration. All cats were monitored for 4 h post-TRH administration for side effects. All 3 TRH doses induced significant TSH (0.01 mg/kg, p = 0.001; 0.05 mg/kg, p = 0.002; 0.1 mg/kg, p = 0.006) and total T4 (0.01 mg/kg, p = 0.008; 0.05 mg/kg, p = 0.006; 0.1 mg/kg, p = 0.001) responses. Lower TRH doses (0.01 and 0.05 mg/kg) caused fewer side effects (1 of 6 cats) than did the highest dose (3 of 6 cats), and may be safer in cats than the previously reported higher dose (0.1 mg/kg) of TRH. Our results do not support the use of maropitant to prevent side effects of a TRH stimulation test in cats.

Assessment of endocrine function in males with pre-diabetes

Introduction and Aim: Diabetes mellitus is associated with various endocrine derangements and prediabetes is an intermediate condition between health and full-fledged disease state. Hormones of Hypothalamus-Pituitary-Thyroid (HPT), Hypothalamus-Pituitary-Adrenal (HPA), Hypothalamus-Pituitary-Gonadal (HPG) axes and pineal gland were studied in males (n=105) with prediabetes.
 
 Materials and Methods: Based on fasting plasma glucose (FPG), the subjects were categorized as healthy controls, prediabetes, diabetes and various hormones were compared between these three groups.
 
 Results: Insulin levels showed a systematic increase from pre-diabetes to diabetes subjects. HPT axis had a semblance to “Primary hypothyroidism” with an increase in Thyrotropin-releasing-hormone (TRH), Thyroid-stimulating-hormone (TSH) and decrease in fT4 and fT3 with rise in glucose levels. HPA axis detected high Corticotropin Releasing Hormone (CRH), Adrenocorticotropic hormone (ACTH), cortisol in the overtly diabetic group while prediabetes values were comparable to control. The HPG axis demonstrated significantly high Gonadotropin-hormone-releasing-hormone (GnRH) in the diabetic group but not in the prediabetic. A graded increase in LH and significant decrease in testosterone and melatonin was observed with a rise in FPG.
 
 Conclusion: Thus, it could be concluded as endocrine gland damage due to hyperglycemia and hyperinsulinemia causes multiple endocrine dysfunctions in prediabetes that aggravates, as the patient turns diabetic.

Regulation of phosphosignaling pathways involved in transcription of cell cycle target genes by TRH receptor activation in GH1 cells

Thyrotropin-releasing hormone (TRH) is known to activate several cellular signaling pathway, but the activation of the TRH receptor (TRH-R) has not been reported to regulate gene transcription. The aim of this study was to identify phosphosignaling pathways and phosphoprotein complexes associated with gene transcription in GH1 pituitary cells treated with TRH or its analog, taltirelin (TAL), using label-free bottom-up mass spectrometry-based proteomics. Our detailed analysis provided insight into the mechanism through which TRH-R activation may regulate the transcription of genes related to the cell cycle and proliferation. It involves control of the signaling pathways for β-catenin/Tcf, Notch/RBPJ, p53/p21/Rbl2/E2F, Myc, and YY1/Rb1/E2F through phosphorylation and dephosphorylation of their key components. In many instances, the phosphorylation patterns of differentially phosphorylated phosphoproteins in TRH- or TAL-treated cells were identical or displayed a similar trend in phosphorylation. However, some phosphoproteins, especially components of the Wnt/β-catenin/Tcf and YY1/Rb1/E2F pathways, exhibited different phosphorylation patterns in TRH- and TAL-treated cells. This supports the notion that TRH and TAL may act, at least in part, as biased agonists. Additionally, the deficiency of β-arrestin2 resulted in a reduced number of alterations in phosphorylation, highlighting the critical role of β-arrestin2 in the signal transduction from TRH-R in the plasma membrane to transcription factors in the nucleus.

The role of leptin resistance in the development of thyroid neoplasia

Background. Leptin influences energy metabolism, as it is able to inform the central nervous system about adipose tissue reserves, and is also an important neuroendocrine regulator. Therefore, an increase in leptin stimulates thyrotropin-releasing hormone secretion, which leads to an increase of thyroid-stimula­ting hormone with normal or slightly elevated levels of thyroxine and triiodothyronine. Leptin imbalance leads to leptin resistance, which develops as a result of impaired sensitivity of hypothalamic receptors to leptin, its penetration through the blood-brain barrier, damage or dysfunction of these receptors, dysfunction of transport proteins accompanied by an increased content of inflammatory mediators that affect leptin receptors and, in turn, damage them. The purpose of the study was to reveal the relationship between hyperleptinemia and leptin resistance in people with different body weight and thyroid nodules. Materials and methods. One hundred and twenty-three patients were examined, who were divided into four groups depen­ding on the body mass index to determine the le­vels of leptin, insulin, and degree of insulin resistance: group 1 — excess body weight (n = 22); group 2 — class 1 obesity (n = 28); group 3 — class 2 obesity (n = 32); group 4 — class 3 obesity (n = 21). The control group consisted of persons with normal body weight (n = 20). Results. It was found that all examined patients had hyperleptinemia (34.5 ng/ml) simultaneously with hyperinsulinemia and insulin resistance (HOMA-IR was 8.3 units). Patients with thyroid neoplasia compared to individuals with normal body weight had significantly higher (by 1.3 times) serum leptin concentrations (p < 0.05; p < 0.001). The research proved that the level of leptine­mia is directly related to the body mass index, waist circumference (r = 0.54; p < 0.001) and hip circumference (r = 0.51; p < 0.001). Conclusions. Among patients with leptin resistance and insulin resistance against the background of obesity of various classes, thyroid neoplasms occur in 28 % of cases. Leptin resistance along with insulin resistance can be considered as independent risk factor for neoplasia. People with abdominal obesity need a mandatory exami­nation of the structural and functional state of the thyroid gland for early detection of nodular neoplasms.

Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.

The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be "sensed" directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.

Genetic link between primary sclerosing cholangitis and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study.

Observational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship between PSC and TD remains uncertain. The purpose of this study is to investigate the causal associations and specific direction between these two conditions. Gaining insight into the potential causal relationship between PSC and TD is valuable for elucidating the pathogenesis of PSC and for devising innovative approaches for the prevention and treatment of PSC and its associated complications. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between PSC and TD, such as autoimmune thyroid disease (AITD), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), among others. PSC was the exposure variable, while TD was the outcome variable. To identify suitable instrumental variables (IVs), we utilized genome-wide association study (GWAS) datasets to select potential candidate single-nucleotide polymorphisms (SNPs). The primary statistical approach employed was the inverse-variance weighted (IVW) method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy. We found that the causal associations between genetically predicted PSC and Graves' disease (GD), hyperthyroidism (IVW OR=1.230, 95%CI: 1.089-1.389, P=0.001; IVW OR=1.001, 95%CI: 1.000-1.002, P=0.000) were statistically significant. The reverse MR analysis indicated that genetic susceptibility to hyperthyroidism (P=0.000) and hypothyroidism (p=0.028) might be the risk of PSC. There was no statistically significant causal association observed between PSC and other TD (IVW P>0.05), with the exception of GD, hyperthyroidism, and hypothyroidism as determined through bidirectional two-sample analysis. To ensure the reliability of our findings, additional sensitivity analyses were conducted, including the leave-one-out (LOO) test, heterogeneity test, and pleiotropic test. In this study, we conducted an investigation into the causal association between PSC and TD. Our findings indicate that PSC significantly elevates the susceptibility to GD and hyperthyroidism from a statistical perspective. These results shed light on the etiology of PSC and have implications for the management of patients with PSC.

Morphofunctional state of the thyroid gland in rats with prolonged low-dose exposure to deltamethrin

The thyroid gland is very sensitive to various stress factors, including chemical ones. Meanwhile, the effect that many ecotoxicants have on the animal endocrine system has not been studied. The effect of cyanide-containing synthetic pyrethroids on the synthesis and secretion of thyroid hormones during prolonged low-dose exposure remains an open question. This research was aimed at assessing the morphofunctional state of the thyroid gland in laboratory rats under the specified exposure regime. The studies were conducted on 48 male Wistar rats. When modeling the effect of low doses of deltamethrin on animals, the substance was administered to rats at a dose of 1/100 LD50, and the experiment lasted for 120 days. The concentrations of thyroid-stimulating hormone, total thyroxine (T4), triiodothyronine (T3), and the ratio T4/T3 were determined in the rats' blood. The solid-phase enzyme immunoassay method was used to determine hormones. For histological examination, the thyroid gland of animals was fixed in a 4% neutral formaldehyde solution. Sections of paraffin blocks were stained with hematoxylin and eosin. Prolonged low-dose exposure to deltamethrin caused hypofunction of the thyroid gland in laboratory rats, which was accompanied by a decrease in the level of thyroid hormones in the blood serum. The stimulating effect of the pituitary gland increased compensatorily due to the additional release of thyroid-stimulating hormone. At the same time, there was a change in the ratio of T4/T3 in the blood. The histological patterns of the thyroid gland were characterized by a decrease in the thyrocyte area, growth of follicles, and colloid densification.

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

FRI471 Regulation Of Adult Thyroid Hormone Homeostasis By Early Postnatal Hyperthyroidism In Male Mice

Abstract Disclosure: D. Kovári: None. A. Szilvásy-Szabó: None. V. Penksza: None. B. Gereben: None. C. Fekete: None. The thyroid hormone (TH) negative feedback regulation enables the hypothalamic-pituitary-thyroid (HPT) axis to maintain the relatively steady circulating TH levels. Internal and external factors influence the development of this feedback regulation and consequently evoke life-long changes of the HPT axis activity. The aim of our study was to reveal how perinatal alteration of TH status influences TH homeostasis of adult mice. Mice were treated with 1µg/bwg thyroxine (T4) or vehicle subcutaneously every day between postnatal day (P) 2-6 and sacrificed at adulthood. Early postnatal hyperthyroidism resulted in central hypothyroidism in adults, characterized by decreased thyrotropin releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and lower serum free T4 level, accompanied by unchanged thyrotropin stimulating hormone β (TSHβ) mRNA expression in the pituitary and serum free triiodothyronine level. The two main regulators of the HPT axis are the hypophysiotropic TRH neurons and tanycytes. Tanycytes affect the feedback regulation of TRH neurons by type 2 deiodinase (D2) mediated TH activation. To understand how postnatal T4 treatment results in central hypothyroidism in adult mice, tanycytes and TRH neurons of the PVN were isolated by laser capture microdissection from control and postnatally T4 treated adult mice. Postnatal T4 treatment did not change D2 expression in the tanycytes. Furthermore, using Thyroid Hormone Action Indicator (THAI) mice, we showed that the treatment did not influence TH action in the mediobasal hypothalamus of adult mice. These data together indicate that tanycytes are not involved in mediation of the postnatal T4 treatment induced effects. In contrast, the early postnatal T4 treatment markedly changed the transcriptome of TRH neurons in the PVN of adult mice. The expression of TH receptors, most TH receptor-related coregulators, TH transporters and genes involved in the synthesis of TRH were decreased. Despite of the central hypothyroidism, the energy expenditure of these mice were not decreased and TH action also remained unchanged in most tissues indicating that the peripheral tissues are able to compensate the effect of the generated mild hypothyroidism. These results indicate that alteration of TH levels during the early postnatal period can cause life-long effects on the activity of the HPT-axis likely via epigenetic regulation of TRH neurons. Presentation: Friday, June 16, 2023

FRI474 Panhypopituitarism And Central Hypothyroidism Presenting As Myoclonus And Hyperreflexia, An Unusual Presentation Likely Related To Thyrotropin-releasing Hormone

Abstract Disclosure: I. Nadeem: None. W.J. Khan: None. S. Thapa: None. Introduction: Panhypopituitarism may present with symptoms of predominantly one or more hormonal deficiencies. The thyrotropin-releasing hormone has been described as causing neuromuscular hyperexcitability via its modifying role in synaptic functions in addition to its effect on the pituitary. We present a panhypopituitarism due to macroadenoma presenting with weakness, tongue fasciculation, hyperreflexia, and myoclonic jerks. Case Presentation: A 78-year-old woman with a medical history of essential hypertension came to ER with generalized weakness, twitching of her tongue, and involuntary jerking movements of her lower limbs for the past month. On admission, vital signs were normal. Neurological examination revealed tongue fasciculation and bilateral lower extremity myoclonus. Her visual field testing was normal. CT scan of the head showed an apparent seller mass but ruled out any acute pathology. Further neurologic, infectious, and rheumatologic work-up revealed negative results. In addition, an MRI of the cervical, thoracic, and lumbar spine was negative for any mass effect. The pituitary showed a 2.0 x 1.5 x 2.3 cm sellar mass, deforming the optic chiasm and deviating the infundibular stalk to the right side. Laboratory work-up revealed secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, and hyperprolactinemia. The patient was diagnosed with non-functioning pituitary macro adenoma. Myoclonus significantly improved after initiating the hormone replacement with levothyroxine and a stress hydrocortisone dose, gradually tapered to a physiological dose, and cabergoline. Repeat MRI after three months showed a stable 1.5 x 2.0 x 2.3 cm sellar mass. Surgery was not recommended due to no visual compromise. Instead, she will be followed in the clinic with a 6-month head imaging and hormone testing. Discussion: Usual clinical manifestations of hypothyroidism are the same regardless of etiology. However, there may be additional findings related to hypothalamic or pituitary dysfunction in the case of secondary or tertiary hypothyroidism due to non-thyroidal illness. Muscle fasciculations are common with hypothyroidism. But myoclonus and hyperreflexia are the findings in hyperthyroidism except for one hypothyroid state, i.e., Hashimoto encephalopathy (HE). TRH plays an important role in the pathophysiology of myoclonus and hyperreflexia in patients with HE and without HE. Our patient had tertiary hypothyroidism with likely elevated TRH in the presence of low FT4 and TSH. Therefore, we propose a high level of TRH in central hypothyroidism as the reason for her hyperreflexia and myoclonus. Presentation: Friday, June 16, 2023

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction

Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID diagnosis.Sixty-three horses were assigned to control (n = 17), subclinical PPID (n = 21) and clinical PPID (n = 25) groups, based on a composite reference standard that combined clinical history and examination findings with endocrine test results. TRH stimulation tests were performed monthly for a 12-month period. Circannual changes were evaluated with one- and two-way repeated-measures analysis of variance and receiver operating characteristic curve analysis was used to derive cut-off values for basal and TRH-stimulated ACTH. TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October. Specificity of both basal and 30 min post-TRH ACTH was generally higher than sensitivity, and TRH stimulation had improved diagnostic accuracy compared to basal ACTH, although its sensitivity was not significantly greater year-round. TRH stimulation tests yielded considerably more positive results than basal ACTH in the subclinical group, but few additional positive results in clinical PPID cases. There were large differences between cut-offs that maximised sensitivity or specificity for TRH-stimulated ACTH, highlighting the importance of considering clinical presentation alongside test results in diagnostic decision-making.

Diagnosis of equine pituitary pars intermedia dysfunction

Equine pituitary pars intermedia dysfunction (PPID) is common in aged horses. The majority of horses respond well to treatment, but treatment is lifelong, meaning accurate diagnosis of PPID is important. Similar to any condition, there is no perfect laboratory test to diagnose PPID and accuracy is affected by the characteristics of the population in which the test is being evaluated. This review details the importance of consideration of clinical factors and diagnostic test accuracy. Basal adrenocorticotrophic hormone (ACTH) concentration is used most frequently in practice and has very good diagnostic accuracy when used in combination with clinical judgement and the correct application of diagnostic thresholds. The thyrotropin-releasing hormone stimulation test can be used in horses with equivocal test results following basal ACTH testing, or to evaluate subtle cases due to its improved accuracy.

Mastication stimuli regulate the heartbeat rate through rhythmic regulation by the hypothalamic-autonomic system; molecular and telemetric studies in weaning-stage rats.

Mastication stimuli have been demonstrated to affect memory function and autonomic nerve activity; however, this process has not been well studied during weaning compared to old age. Previously, we conducted molecular analyses of the thalamus and hippocampus to elucidate the mechanisms underlying this memory-enhancing effect in weaning-stage rats. In this study, we aimed to evaluate the effect of masticatory stimuli on the regulation of heartbeat rate (HR) through the hypothalamic-autonomic system. Three-week-old male rats were administered a powdered diet (P group) or chow-diet (C group) for 10 days. Thereafter, transcriptome analysis was performed. Vasopressin, cocaine-amphetamine-regulated transcript prepropeptide, corticotropin-releasing hormone, and thyrotropin-releasing hormone, which are involved in sympathetic activation of heart rate, were downregulated in the C group. Electrocardiograms were recorded continuously for 12 days under the same condition. Interestingly, rats in the C group had a significantly lower HR than those in the P group on day 11. We checked several parameters representing the autonomic regulation of HR. The C group had higher values for the high-frequency band integration of the HR power spectrum (parasympathetic marker) and root mean square successive difference of R-wave intervals (parasympathetic marker) relative to the P group. Such findings provide a molecular and physiological basis for understanding the regulation of cardiovascular function in response to masticatory stimuli in the autonomic nervous system.

Modelling the Effect of the Exposure to Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) on Thyroid Homeostasis

Thyroid homeostasis is crucial for the human body. The imbalance of thyroid homeostasis might cause diseases such as hypothyroidism. Humans are exposed to PFOS/PFOA frequently since they have been used in various industrial products. As reported that PFOS/PFOA increase the metabolic clearance rate of thyroid hormones, we then develop a mathematical model in terms of a system of differential equations to investigate thyroid homeostasis based on the changes in the levels of thyrotropin-releasing hormone, thyroid-stimulating hormone and thyroid hormones when the effect of the exposure to PFOS and PFOA is also incorporated as well. The geometric singular perturbation technique is then employed to identify the possible dynamic behaviours obtained from the model. Numerical investigations are also presented to illustrate the results from theoretical analysis. Both theoretical and numerical results imply that a periodic behaviour that has been observed clinically in the pulsatile secretions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone could be obtained from our model. In addition, the numerical experiment also shows that the levels of thyroid hormones and thyroid-stimulating hormone for the case when there is the effect of exposure to PFOS and PROA are lower than those of the case when there is no effect of the exposure to PFOS and PFOA which might lead to the imbalance of thyroid homeostasis.

Effects of sub-chronic exposure to microcystin-LR on the endocrine system of male rats

Microcystins (MCs) can cause reproductive and developmental toxicity and disrupt endocrine homeostasis in mammals. In the present study, male, Sprague-Dawley (SD) rats were administrated 3 or 30 μg MC-LR/kg, body mass (bm) per day via intraperitoneal (i.p.) injections for 6 weeks. Effects of MC-LR on histology, hormone concentrations, gene transcriptional profiles and protein expressions along the hypothalamic-pituitary-adrenal (HPA), ‐gonad (HPG) and -thyroid (HPT) axes were assessed. Sub-chronic administration with MC-LR caused histological damage to hypothalamus, pituitary, adrenal, testes and thyroid and affected relative masses of pituitary, adrenal and testes. The HPA axis was activated and serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were significantly augmented. Along the HPG axis, serum concentrations of gonadotropin-releasing hormone (GnRH) and dihydrotestosterone (DHT) were diminished, while concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) were augmented. For the HPT axis, only concentrations of free tetra-iodothyronine (fT4) were significantly diminished, while concentrations of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH) or free tri-iodothyronine (fT3) were not significantly changed. Also, several genes and proteins related to synthesis of steroid hormones were significantly altered. Findings of the present study illustrate that MC-LR can cause endocrine-disrupting effects through the disruption of synthesis and secretion of hormones along the HPA, HPG and HPT axes and negative feedback regulation. Also, there could be crosstalk among HPA, HPG and HPT axes. These findings elucidate mechanisms of endocrine-disrupting effects of MCs.