Thyrotropin-releasing Hormone Levels Research Articles

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.

Heat exposure alters the mRNA expression of growth- and stress-related genes in chicks

High ambient temperature, a major stressor, impairs the growth of chickens. In this study, we examined the effect of heat exposure on the mRNA expression of various growth related genes, such as growth hormone (GH), insulin-like growth factor-1 (IGF1), GH-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), and somatostatin (SST) in layer-type chickens (Gallus gallus domesticus) at an early age. In addition, we examined the reactivity of the corticotrophin-releasing hormone (CRH) system, one of the stress-regulating pathways, to heat exposure and its role in altering the growth related genes. Four-day heat exposure reduced the body weight gain, feed intake, and feeding efficiency and increased the rectal temperature of chicks (P<0.05). The mRNA expression levels of pituitary GH, liver IGF1, and diencephalic GHRH decreased with heat exposure (P<0.05) whereas the levels of TRH or SST did not change. Heat exposure also reduced the diencephalic mRNA expression level of CRH and increased pituitary CRH receptor-2 mRNA and the plasma corticosterone (CORT) concentration (P<0.05), suggesting that heat exposure affected the hypothamic-pituitary adrenal gland (HPA) axis. Similar to the heat-exposure study, subcutaneous injection of CORT for 4 days decreased body weight, and the mRNA expression of pituitary GH and liver IGF1 (P<0.05). The present study demonstrated that heat exposure reduced the mRNA expressions of pituitary GH and liver IGF1, and suggested that the change in mRNA expression may have been partly caused by CORT.

The effect of red ginseng and ginseng leaves on the substance and energy metabolism in hypothyroidism rats

BackgroundRecent studies have revealed that the properties Traditional Chinese Medicine is mostly associated with are substance and energy metabolism. Our study aimed to compare the effect of red ginseng (RG) (warm property) and ginseng leaves (GL; cold property) on the substance and energy metabolism of rats with hypothyroidism. Materials and methodsRats were administered propylthiouracil intraperitoneally for 20 d to cause hypothyroidism. The reference group was orally administered Aconiti Lateralis Radix Praeparaia [FZ (Fuzi in Chinese)], while both the RG and GL groups were orally administrated crude drugs. The rectal, tail, toe, and axilla temperature of the rats were assayed every 3 d. Oxygen consumption, carbon dioxide production, heat production, and energy expenditure were measured via TSE phenoMaster/LabMaster animal monitoring system. Adenosine monophosphate-activated protein kinase, Na+-K+-ATPase, fumarase, pyruvic acid and cyclic adenosine monophosphate/cyclic guanosine monophosphate were determined. ResultsThe lower levels of triiodothyronine, tetraiodothyronine, and thyrotropin-releasing hormone and the higher level of thyroid stimulating hormone revealed the successful establishment of a hypothyroidism model. Oxygen consumption, carbon dioxide production, heat production, and energy expenditure in the FZ and RG groups were obviously increased. The activity of Na+-K+-ATPase and fumarase in the FZ and RG groups was significantly increased. The cyclic adenosine monophosphate/cyclic guanosine monophosphate level in the FZ and RG groups was increased, while the GL group showed the opposite. ConclusionOur research provides a new way to explore the efficiency of Chinese medicine on the basis of the relationship between drug property and effects on substance and energy metabolism.

Exposure of Pregnant Mice to Perfluorobutanesulfonate Causes Hypothyroxinemia and Developmental Abnormalities in Female Offspring.

Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice.

Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol.

Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p < .05), whereas the CDD patients performed poorly in all the assessed memory types (p < .05). In addition, the CID patients had higher levels (mean difference [95% CI]) of corticotrophin-releasing hormone, cortisol (31.98 [23.97, 39.98] μg/l), total triiodothyronine (667.58 [505.71, 829.45] μg/l), and total thyroxine (41.49 [33.23, 49.74] μg/l) (p < .05), and lower levels of thyrotropin-releasing hormone (-35.93 [-38.83, -33.02] ng/l), gonadotropin-releasing hormone (-4.50 [-5.02, -3.98] ng/l) (p < .05), and adrenocorticotropic hormone compared to the CDD patients. After controlling for confounding variables, the partial correlation analysis revealed that the levels of cortisol positively correlated with the errors in object working memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels.

DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats.

Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones.

Chronic Tension Type Headache, An Analog for Fibromyalgia and Depression Disorder?

Background: Chronic tension type headache (CTTH) is the most prevalent headache and is associated with a high socio-economic impact. The exact pathogenesis of CTTH remains unclear. It has been shown CTTH has many similar clinic features with fibromyalgia (FM) and major depression disorder (MDD). Several studies have found some changes of hypothalamic-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes, sex hormones and pro-inflammatory cytokines in FM and MDD. We speculated CTTH has the same changes. Striving to provide new insights into the pathophysiology of CTTH, we designed this trial to address the common and specific aspects of these three disorders in their clinic features and pathophysiological mechanisms, especially from neuroendocrine system and inflammatory pathways. Method: The patients with CTTH, FM and MDD were recruited, and the healthy subjects were selected as controls. The sleep quality, depressive mood and cognitive function of all subjects were evaluated. The serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, thyrotrophin releasing hormone (TRH), thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4) , gonadotrophin releasing hormone (GnRH), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected to find the changes of neuroendocrine system and inflammatory pathways which are believed to be linked with these disorders. Results: Compared with the controls, the HAMD-17 and PSQI scores were significantly higher (Ps<0.001) and the MoCA-C score was significantly lower (P=0.029) in the CTTH, FM and MDD patients. The patients with the CTTH, FM and MDD showed different degrees of damage in spatial and object memories compared to the controls (Ps<0.05). The changes of the HPA and HPT axes, GnRH and pro-inflammatory cytokines in the CTTH, FM and MDD patients were similar. In addition, the serum levels of CRH, cortisol, GnRH, TRH, IL-1β and TNF-α were significantly higher (P<0.001) while TT3, TT4 were significantly lower (P<0.001) in the CTTH, FM and MDD groups relative to the controls. The FM patients showed lower value in the pituitary level of HPA and HPT axis. Conclusion: The patients with CTTH had similar patterns of memory damage and changes of the HPA and HPT axes, GnRH and pro-inflammatory cytokines with the FM and MDD patients.

Effect of Short-Term Thermal Conditioning on Physiological and Behavioral Responses to Subsequent Acute Heat Exposure in Chicks

It is known that thermal conditioning at an early age results in improved heat tolerance, and reduces mortality when re-exposed to heat in later life in chickens. However, the mechanism of thermal conditioning is not fully understood. The objective of this study was to investigate the effect of early thermal conditioning on physiological and behavioral responses in acute heat-exposed chicks. Six-day-old chicks (White Plymouth Rock) were exposed to high temperature at 40°C for 3 h while control chicks were kept at 30°C. Four days after treatment, both groups were challenged to high temperature at 40°C for 15min. We found that the initiation times for behavioral responses (panting and wing-droop posture) in experienced chicks were later than those in control. At the end of heat-exposure treatment, the rectal temperature in experienced chicks was lower than that in control while there was no difference in respiration rate between the groups. Compared with control, experienced chicks had a lower level of plasma corticosterone. Gene expression levels of brain-derived neurotrophic factor, thyrotropin-releasing hormone, interleukin6 and lipopolysaccharide-induced tumor necrosis factor were significantly lower in the brain of experienced chicks than in the control chicks. These results suggest that thermal conditioning may change response to subsequent heat exposure by altering the central thermoregulation system, resulting in an alleviation of heat stress.

Hormonal contraception with progestagen desogestrel in women with diffuse non-toxic goiter аnd autoimmune thyroiditis

The article represents influence of gestagen desogestrel on size and function of thyroid gland in women of reproductive age. Into the study we included 70 women who were prescribed gestagen desogestrel in a daily dose of 75 mg for a period of 12 months. All the patients were devided into two groups. The first group consisted of 20 women with diffuse nontoxic goiter, the second consisted of 30 women with autoimmune thyroiditis. Control group consisted of 20 women without thyroid gland pathology. Prior to therapy with desogestrel and after 12 month of treatment, serum levels of free triiodothyronine, free thyroxine and thyrotropin releasing hormone, thyroperoxidase antibodies were determined and thyroid gland sonigraphy was performed in all the patients. Obtained data show that gestagen desogestrel doesn’t influence the size and function of thyroid gland in healthy women and in patients with diffuse non-toxic goiter. In women with autoimmune thyroiditis implication of desogestrel significantly decreases blood levels of thyroperoxidase autoantibodies.

Effects of food deprivation on the hypothalamic feeding-regulating peptides gene expressions in serotonin depleted rats

We examined the effects of serotonin (5-HT) depletion induced by peripheral injection of 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) on the expression of feeding-regulating peptides expressions by using in situ hybridization histochemistry in adult male Wistar rats. PCPA pretreatment had no significant effect on basal levels of oxytocin, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), neuropeptide-Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin in the hypothalamus. Food deprivation for 48h caused a significant decrease in CRH, TRH, POMC, and CART, and a significant increase in NPY, AgRP and MCH. After PCPA treatment, POMC and CART did not decrease despite food deprivation. NPY was significantly increased by food deprivation with PCPA, but was attenuated compared to food deprivation without PCPA. These results suggest that the serotonergic system in the hypothalamus may be involved in the gene expression of POMC, CART, and NPY related to feeding behavior.

Hormonal contraception in women with diffuse nontoxic goiter and autoimmune thyroiditis

The article considers the influence of combined oral contraceptives on size and function of thyroid gland in women of reproductive age. We examined 215 women, taking low dose and microdose combined oral contraceptives for 12 months as monotherapy or in combination with potassium iodide. The first group consisted of 75 women with diffuse nontoxic goiter, second – of 70 women with autoimmune thyroiditis. Control group consisted of 70 women without pathology of thyroid gland. Prior to therapy with combined contraceptives and after 12 months of treatment, we determined serum levels of free triiodothyronine, free thyroxine, and thyrotropin releasing hormone, antibodies to thyroid peroxidase and antibodies to thyroglobulin (ELISA) and performed sonography of thyroid gland. Results of our study suggest that combined oral contraceptives may increase the size of thyroid gland among women with diffuse nontoxic goiter without changing its function. In women with autoimmune thyroiditis, application of combined oral contraceptive significantly decreases blood levels of autoantibodies to thyroid peroxidase and thyroglobulin. Application of combined oral contraceptives in healthy women doesn’t influence the size and function of thyroid gland.

Alterations in Hypothalamus-Pituitary-Adrenal/Thyroid Axes and Gonadotropin-Releasing Hormone in the Patients with Primary Insomnia: A Clinical Research

The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes’ hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman’s correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the “stepwise” method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.

Nesfatin‐1, corticotropin‐releasing hormone, thyrotropin‐releasing hormone, and neuronal histamine interact in the hypothalamus to regulate feeding behavior

Nesfatin-1, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and hypothalamic neuronal histamine act as anorexigenics in the hypothalamus. We examined interactions among nesfatin-1, CRH, TRH, and histamine in the regulation of feeding behavior in rodents. We investigated whether the anorectic effect of nesfatin-1, α-fluoromethyl histidine (FMH; a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine), a CRH antagonist, or anti-TRH antibody affects the anorectic effect of nesfatin-1, whether nesfatin-1 increases CRH and TRH contents and histamine turnover in the hypothalamus, and whether histamine increases nesfatin-1 content in the hypothalamus. We also investigated whether nesfatin-1 decreases food intake in mice with targeted disruption of the histamine H1 receptor (H1KO mice) and if the H1 receptor (H1-R) co-localizes in nesfatin-1 neurons. Nesfatin-1-suppressed feeding was partially attenuated in rats administered with FMH, a CRH antagonist, or anti-TRH antibody, and in H1KO mice. Nesfatin-1 increased CRH and TRH levels and histamine turnover, whereas histamine increased nesfatin-1 in the hypothalamus. Immunohistochemical analysis revealed H1-R expression on nesfatin-1 neurons in the paraventricular nucleus of the hypothalamus. These results indicate that CRH, TRH, and hypothalamic neuronal histamine mediate the suppressive effects of nesfatin-1 on feeding behavior.

Leptin as a Modulator of Neuroendocrine Function in Humans

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.

Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients

The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light-dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep-wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.

Thyroid hormone regulation by stress and behavioral differences in adult male rats

Thyroid hormones are essential regulators of growth, development and normal bodily function and their release is coordinated by the hypothalamic–pituitary–thyroid (HPT) axis. While the HPT axis has been established as an acutely stress-responsive neuroendocrine system, relatively little is known about the mechanisms of its stress regulation. The present study examined acute stress-induced changes in peripheral hormone levels [triiodothyronine (T3); thyroxine (T4), thyroid-stimulating hormone (TSH), reverse triiodothyronine (rT3)] and central mRNA levels of regulators of the HPT axis [thyrotropin-releasing hormone (TRH), somatostatin (SST), type II deiodinase (D2)] in response to an inescapable tail-shock, a rodent model of stress. Additionally, we examined whether individual differences in spontaneous exploratory behavior in an open field test predicted basal levels of TH or differential susceptibility to the effects of stress. The stress condition was associated with decreases in peripheral T3, T4 and TSH, but not rT3, when compared with controls. No changes were observed in TRH or SST mRNA levels, but there was a trend suggesting stress-related increases in D2 mRNA. We also found that an animal's exploratory behavior in an unfamiliar open field arena was positively related to peripheral thyroid hormone levels and predicted the magnitude of stress-induced changes.In conclusion, we found suggestive evidence for stress-induced decrease in central drive HPT axis, but the central mechanisms of its stress regulation remain to be elucidated. Additionally, we found that individual differences in animals' exploratory behavior were correlated with peripheral TH levels.

Pituitary Hyperplasia Secondary to Hypothyroidism Caused by Hashimoto's Thyroiditis in a Female Adolescent

Pituitary enlargement secondary to primary hypothyroidism is a known but uncommon occurrence and is difficult to distinguish on computed tomography (CT) and magnetic resonance imaging (MRI) from primary pituitary tumor. The lack of thyroxine feedback found in uncontrolled primary hypothyroidism leads to elevated levels of thyrotropin-releasing hormone (TRH), which causes both pituitary thyrotroph and lactotroph hyperplasia, increasing the secretion of both thyroidstimulating hormone (TSH) and prolactin. With long-standing hypothyroidism, thyrotroph hyperplasia can result in expansion of the sella turcica and enlargement of the pituitary gland. Pituitary hyperplasia usually regresses following adequate treatment with hormone replacement over a period of a few months. We herein report a case of pituitary hyperplasia associated with hypothyroidism in a short statured female adolescent without the typical clinical features associated with hypothy-

Thyrotropin Releasing Hormone (TRH) in goldfish ( Carassius auratus): Role in the regulation of feeding and locomotor behaviors and interactions with the orexin system and cocaine- and amphetamine regulated transcript (CART)

TRH is a peptide produced by the hypothalamus which major function in mammals is the regulation of TSH secretion by the pituitary. In fish, TRH does not appear to affect TSH secretion, suggesting that it might regulate other functions. In this study, we assessed the effects of central (intracerebroventricular, icv) injections of TRH on feeding and locomotor behavior in goldfish. TRH at 10 and 100 ng/g, but not 1 ng/g, significantly increased feeding and locomotor behaviors, as indicated by an increase in food intake and in the number of total feeding acts as compared to saline-injected fish. In order to assess possible interactions between TRH and other appetite regulators, we examined the effects of icv injections of TRH on the hypothalamic expression of orexin, orexin receptor and CART. The mRNA expression levels of all three peptides were significantly increased in fish injected with TRH at 100 ng/g as compared to saline-injected fish. Fasting increased TRH, orexin, and orexin receptor hypothalamic mRNA levels and decreased CART hypothalamic mRNA levels. Our results suggest that TRH is involved in the regulation of feeding/locomotor activity in goldfish and that this action is associated with a stimulation of both the orexin and CART systems.

The systemic inhibition of nitric oxide production rapidly regulates TRH mRNA concentration in the paraventricular nucleus of the hypothalamus and serum TSH concentration. Studies in control and cold-stressed rats

Neurons of the paraventricular nuclei of the hypothalamus (PVN) that synthesize the peptide thyrotropin releasing hormone (TRH) control energy homeostasis. Identifying the circuits which regulate these neurons is critical to fully understand integration of metabolic information and the mechanisms that set thyroid hormone levels. We tested the hypothesis that nitric oxide (NO) acutely controls PVN TRH expression and thyrotropin (TSH) secretion by the anterior pituitary. The subcutaneous treatment of rats with NG-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthases, enhanced PVN TRH mRNA and medio-basal hypothalamic TRH levels, and reduced serum TSH concentration. Analysis of the effect of a NO donor in primary cultures of hypothalamic or anterior pituitary cells suggested that the effect of NO includes a direct action on hypothalamic neurons. The cold stress-induced increase in TSH release was inhibited by sc l-NAME. Therefore, production of NO may control the activity of the hypothalamus–pituitary–thyroid axis.

Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3β inhibitor

Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant-like neuropeptide that reduces the expression of glycogen synthase kinase-3β (GSK-3β), an enzyme that hyperphosphorylates tau and is implicated in bipolar disorder, diabetes and Alzheimer's disease. In order to understand the potential role of GSK-3β in the modulation of depression by TRH and TRH-like peptides and the therapeutic potential of GSK-3β inhibitors for neuropsychiatric and metabolic diseases, young adult male Sprague–Dawley (SD) rats were (a) injected ip with 1.8 mg/kg of GSK-3β inhibitor VIII (GSKI) and sacrificed 0, 2, 4, 6, and 8 h later or (b) injected with 0, 0.018, 0.18 or 1.8 mg/kg GSKI and bled 4 h later. Levels of TRH and TRH-like peptides were measured in various brain regions involved in mood regulation, pancreas and reproductive tissues. Large, 3–15-fold, increases of TRH and TRH-like peptide levels in cerebellum, for example, as well as other brain regions were noted at 2 and 4 h. In contrast, a nearly complete loss of TRH and TRH-like peptides from testis within 2 h and pancreas by 4 h following GSKI injection was observed. We have previously reported similar acute effects of corticosterone in brain and peripheral tissues. Incubation of a decapsulated rat testis with either GSKI or corticosterone accelerated release of TRH, and TRH-like peptides. Glucocorticoids, via inhibition of GSK3-β activity, may thus be involved in the inhibition of TRH and TRH-like peptide release in brain, thereby contributing to the depressogenic effect of this class of steroids. Corticosterone-induced acceleration of release of these peptides from testis may contribute to the decline in reproductive function and redirection of energy needed during life-threatening emergencies. These contrasting effects of glucocorticoid on peptide release appear to be mediated by GSK-3β.