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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sites at which TRH produces suppression on feeding and drinking were examined anatomically in the rat brain. This was accomplished by microinjecting nmol concentration of TRH into 6 different brain sites. Intracerebroventricular injection of TRH (25, 50, 100 nmol/rat) suppressed starvation-induced feeding and drinking in a dose related manner. The microinjection in a small amount of TRH (8 nmol/hemisphere) into the medial and lateral hypothalamus produced relatively severe anorexia and adipsia as compared with the other areas including the nucleus accumbens, the substantia nigra, the globus pallidus and the amygdala. It was concluded that the medial hypothalamus is the most sensitive site of TRH-induced anorexia and adipsia and the action of TRH on the lateral hypothalamus is also a possible mechanism mediating the decrease in water intake.
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PMID:Intracranial injection of thyrotropin releasing hormone (TRH) suppresses starvation-induced feeding and drinking in rats. 681 81

The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate-limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.
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PMID:Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland. 779 20

It is well recognized that starvation and malnutrition are associated with a low-T3 syndrome in man. A similar condition has been observed after intake of a low carbohydrate hypocaloric diet. However, little is known about the influence of iodine on these conditions. Therefore, we evaluated the effect of iodine supplementation on thyroid function before and after a short-term intake of a low carbohydrate diet in normal subjects residing in an iodine-deficient area. The study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5 females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4 days. Eight subjects received 500 micrograms iodine (oral) daily beginning 4 weeks before diet. The control group (n = 8) received no iodine. After iodine supplementation, iodine excretion increased from 52 to 405 micrograms iodine/g of creatinine. Total T4 showed a slight but significant increase (104.2 nmol/l vs. 115.8 micrograms/dl; p < 0.001); fT4 was unchanged. The intake of the hypocaloric low carbohydrate diet resulted in a striking decrease in both total and free T3 and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were not affected in either group. During diet, iodine administration resulted in a decrease of basal TSH from 2.3 to 1.2 mU/l (p < 0.05), delta TSH from 10.3 to 4.5 mU/l (p < 0.01) and delta T3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects. 826 74

The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.
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PMID:Effects of long-term food reduction on the hypothalamus-pituitary-thyroid axis in male and female rats. 886 83

Prolonged fasting is associated with a number of changes in the thyroid axis manifested by low serum T3 and T4 levels and, paradoxically, low or normal TSH. This response is, at least partly, caused by suppression of proTRH gene expression in neurons of the hypothalamic paraventricular nucleus (PVN) and reduced hypothalamic TRH release. Because the fall in thyroid hormone levels can be blunted in mice by the systemic administration of leptin, we raised the possibility that leptin may have an important role in the neuroendocrine regulation of the thyroid axis, through effects on hypophysiotropic neurons producing proTRH. Adult male, Sprague-Dawley rats were either fed normally, fasted for 3 days, or fasted and administered leptin at a dose of 0.5 microg/gm BW i.p. every 6 h. Fasted animals showed significant reduction in plasma total and free T4 and T3 levels compared with controls, that were restored toward normal by the administration of leptin. Percent free T4, but not percent free T3, increased during fasting, further suggesting a reduction in plasma transthyretin levels that did not return to fed levels after leptin administration. By semiquantitative analysis of in situ hybridization autoradiograms, proTRH messenger RNA in medial parvocellular PVN neurons was markedly suppressed in the fasting animals but was restored to normal by leptin administration [fed vs. fast vs. fast/leptin (density units x 10(8)): 8.5 +/- 0.4, 3.2 +/- 0.2, 8.1 +/- 0.8]. In contrast, proTRH messenger RNA in adjacent neurons in the lateral hypothalamus that do not have a hypophysiotropic function remained unchanged by any of the experimental manipulations. These findings indicate that leptin has a selective, central action to modulate the hypothalamic-pituitary-thyroid axis by regulating proTRH gene expression in the PVN but does not have peripheral effects on thyroid-binding proteins. We propose that the fall in circulating leptin levels during fasting resets the set point for feedback inhibition by thyroid hormones on the biosynthesis of hypophysiotropic proTRH, thereby allowing adaptation to starvation.
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PMID:Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. 916 50

Gene expression for agouti-related protein (AGRP), an endogenous antagonist of melanocortin receptors, has been localized to the hypothalamic arcuate nucleus, where it colocalizes with neuropeptide Y (NPY). Having reported that the NPY innervation of hypophysiotropic TRH neurons in the hypothalamic paraventricular nucleus (PVN) originates primarily from NPY-producing neurons in the arcuate nucleus, here we examined the possibility that TRH neurons in the PVN are similarly innervated by AGRP nerve terminals. Using immunohistochemistry, AGRP-containing cell bodies were found almost exclusively in the arcuate nucleus, but their projections were distributed widely in the hypothalamus, most conspicuously in the paraventricular (PVN), arcuate and dorsomedial nuclei, and the posterior hypothalamic area. Ablation of the arcuate nucleus by the neonatal administration of monosodium glutamate obliterated nearly all AGRP-immunoreactivity in the hypothalamus. In the PVN, double-labeling light and electron microscopic immunohistochemistry revealed that TRH neurons receive dense innervation by AGRP nerve terminals, with the frequent occurrence of axosomatic and axodendritic synapses (mainly of the symmetrical type). These findings provide morphological basis to hypothesize a role for AGRP in the arcuato-paraventricular pathway, in the down-regulation of the hypothalamic-pituitary-thyroid axis, which occurs as an adaptive response to starvation.
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PMID:Agouti-related protein containing nerve terminals innervate thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. 1043 22

The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and falling levels of leptin are a critical signal for this adaptation, acting to suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the paraventricular nucleus of the hypothalamus. This study addresses the mechanism for this regulation, using primary cultures of fetal rat hypothalamic neurons as a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH biosynthesis, with a maximum response at 10 nm. TRH release was quantified using immunoprecipitation, followed by isoelectric focusing gel electrophoresis and specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold. Immunocytochemistry revealed that a substantial population of cells expressed TRH or leptin receptors and that 8-13% of those expressing leptin receptors coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV-1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA. Although the above data are consistent with a direct ability of leptin to promote TRH biosynthesis through actions on TRH neurons, addition of alpha-melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the neuronal culture. Consequently, our data suggest that leptin regulates the TRH neurons through both direct and indirect pathways.
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PMID:Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways. 1096 95

Melanin-concentrating hormone (MCH) is an orexigenic peptide encoded in the pre-pro MCH gene. Targeted deletion of MCH causes a phenotype of hypophagia and leanness with an inappropriately high metabolic rate, suggesting a role for MCH in the control of energy balance. In order to further elucidate the mechanism by which MCH controls, energy expenditure, we have investigated the effects of MCH on the hypothalamic pituitary thyroid (HPT) axis. The thyroid axis is important in energy homeostasis and starvation leads to profound suppression of the HPT axis. MCH significantly reduces plasma TSH in vivo at 10 min (0.5 +/- 0.07 ng/ml, p < 0.05, n = 8) and 60 min (0.33 +/- 0.04 ng/ml, p < 0.01, n = 10) compared to saline (0.7 +/- 0.07 ng/ml and 0.69 +/- 0.07 ng/ml respectively) when administered intracerebroventricularly. Release of TRH form hypothalamic explants was significantly reduced in the presence of MCH production (7.1 +/- 0.99 fmol/explant to 2.3 +/- 0.4 fmol/explant p < 0.01, n = 18) and Neuropeptide EI (NEI) (8.47 +/- 1.28 fmol/explant to 4.6 +/- 1.13 p < 0.05, n = 16), a peptide, also encoded in the pre-pro-MCH gene. MCH was also shown to significantly reduce TRH stimulated TSH release from dispersed pituitary cell cultures (basal = 0.5 +/- 0.06 ng/ml, 100 nM TRH = 0.9 +/- 0.2 ng/ml, p < 0.05 0.1 nM MCH = 0.5 +/- 0.1 ng/ml, p < 0.05, 1 nM MCH = 0.3 +/- 0.03 ng/ml, p < 0.01, 10 nM MCH = 0.4 +/- 0.02 ng/ml, p < 0.01, 1000 nM MCH = 0.4 +/- 0.05 ng/ml, P < 0.01, n = 4), although basal release of TSH from these cultures was unaffected. These data suggest a possible role for MCH in the control of energy homeostasis via inhibition of the thyroid axis.
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PMID:Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone (TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary. 1141 52

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.
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PMID:Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. 1205 88

During starvation in rodents, the hypothalamic-pituitary-thyroid axis is down-regulated, resulting in low circulating thyroid hormone levels. This involves a reduction in hypothalamic TRH mRNA that is caused in part by a fall in serum leptin levels, which is sensed by neurons within the hypothalamus. The mechanism by which this regulation occurs is not fully understood. Here we show transfection data and in vivo evidence, suggesting that leptin can regulate trh gene expression via activation of intracellular signal transducer and activator of transcription 3 (STAT3) proteins in TRH neurons. In trh promoter assays using transfected cells, functional STAT3 proteins are required for maximal activation of the trh promoter by leptin. Consistent with this, the STAT3-binding site on the leptin receptor is also required for this regulation. Using double immunohistochemistry, we show that peripherally administered leptin rapidly stimulates STAT3 phosphorylation in approximately 40% of TRH neurons in the paraventricular nucleus of the hypothalamus (PVN) in rats. Detailed anatomical analyses reveal that the leptin-responsive TRH neurons are concentrated in the caudal region of the medial and periventricular parvocellular subnucleus of the PVN. Combined, our data show that only a subpopulation of TRH neurons in the PVN is leptin responsive and suggest that stimulation of hypothalamic trh gene expression by leptin involves activation of STAT3 and that this signaling pathway is important for regulation of the hypothalamic-pituitary-thyroid axis by leptin.
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PMID:Role of signal transducer and activator of transcription 3 in regulation of hypothalamic trh gene expression by leptin. 1476 29


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