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

Dietary restriction reduces circulating gonadotropin and testosterone levels in male rats, an effect thought to be mediated through reduced gonadotropin-releasing hormone (GnRH) secretion; however, the cellular mechanisms subserving this response are still unknown. We reasoned that if dietary restriction reduces GnRH secretion, this would be reflected by a decrease in GnRH synthesis and likewise cellular GnRH mRNA levels. We tested this hypothesis by comparing cellular levels of GnRH mRNA between ad libitum fed (n = 4) and starved (n = 4) adult male rats. Five days of starvation resulted in a 21% decrease in body weight and an 85% decline in serum testosterone levels (fed: 13.9 +/- 2.00 vs. starved: 2.1 +/- 0.70 nmol/l; p < 0.01). In situ hybridization and image analysis demonstrated that short-term starvation influenced neither GnRH cell number (fed: 148 +/- 16 vs. starved: 157 +/- 13 cells) nor cellular GnRH mRNA signal level (fed: 177 +/- 5 vs. starved: 160 +/- 7 grains/cell) in any region of the basal forebrain. Endogenous opioid peptides are known to exert an inhibitory effect on GnRH secretion and have been implicated in having a role in the starvation-induced effects on the reproductive system. We therefore also tested the hypothesis that alterations in proopiomelanocortin (POMC) gene expression are involved in the neuroendocrine response to starvation, by comparing cellular POMC mRNA levels in individual neurons (approximately 160 neurons/animal) of the arcuate and periarcuate nuclei between fed control (n = 4) and starved (n = 4) adult male rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short-term starvation decreases POMC mRNA but does not alter GnRH mRNA in the brain of adult male rats. 136 2

Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.
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PMID:A review of endocrine changes in anorexia nervosa. 1022 46

We have investigated the hormonal and hypothalamic neuropeptidergic substrates of dehydration-associated anorexia. In situ hybridization and hormone analyses of anorexic and paired food-restricted rats revealed two distinct profiles. First, both groups had the characteristic gene expression and endocrine signatures usually associated with starvation: increased neuropeptide Y and decreased proopiomelanocortin and neurotensin mRNAs in the arcuate nucleus (ARH); increased circulating glucocorticoid but reduced leptin and insulin. Dehydrated animals are strongly anorexic despite these attributes, showing that the output of leptin- and insulin-sensitive ARH neurons that ordinarily stimulate eating must be inhibited. The second pattern occurred only in anorexic animals and had two components: (1) reduced corticotropin-releasing hormone (CRH) mRNA in the neuroendocrine paraventricular nucleus (PVH) and (2) increased CRH and neurotensin mRNAs in the lateral hypothalamic (LHA) and retrochiasmatic areas. However, neither corticosterone nor suppressed PVH CRH gene expression is required for anorexia after dehydration because PVH CRH mRNA in dehydrated adrenalectomized animals is unchanged from euhydrated adrenalectomized controls. We also showed that LHA CRH mRNA was strongly correlated with the intensity of anorexia, increased LHA CRH gene expression preceded the onset of anorexia, and dehydrated adrenalectomized animals (which also develop anorexia) had elevated LHA CRH gene expression with a distribution pattern similar to intact animals. Finally, we identified specific efferents from the CRH-containing region of the LHA to the PVH, thereby providing a neuroanatomical framework for the integration by the PVH of neuropeptidergic signals from the ARH and the LHA. Together, these observations suggest that CRH and neurotensin neurons in the LHA constitute a novel anatomical substrate for their well known anorexic effects.
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PMID:Distinct patterns of neuropeptide gene expression in the lateral hypothalamic area and arcuate nucleus are associated with dehydration-induced anorexia. 1040 47

Starvation induces a decrease in circulating leptin levels and activation of the hypothalamus-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis in unfed rodents or genetically leptin-deficient ob/ob mice, whereas it stimulates corticotropin-releasing hormone (CRH) gene expression in the paraventricular nucleus (PVN). However, the interactions between leptin, CRH and the HPA axis are poorly understood and are likely to be complex. We recently demonstrated that central leptin administration caused increases in plasma arginine-vasopressin (AVP) and AVP gene expression of the PVN in nonstressful rats. AVP stimulates the release of adrenocorticotropic hormone (ACTH), but it also potentiates the action of CRH on ACTH release. In this study, we investigated the effects of leptin on plasma ACTH and corticosterone levels, CRH mRNA of the PVN and proopiomelanocortin (POMC) mRNA of the pituitary in nonstrained rats. Intracerebroventricularly administered leptin caused increases in plasma ACTH and corticosterone levels in dose-dependent manners. In Northern blot analyses, the leptin injection induced significant increases in the expression of CRH mRNA in the PVN and POMC mRNA in the pituitary. The increased plasma ACTH and corticosterone levels by leptin were attenuated with intracerebroventricular pretreatment of a V(1a) receptor antagonist (OPC-21268) or a V(1a)/V(1b) receptor antagonist (dP[Tyr(Me)(2)]AVP), but not with that of a V(2) receptor antagonist (OPC-31260). The leptin-induced CRH mRNA expression in the PVN and POMC mRNA expression in the pituitary were also reduced by the pretreatment with OPC-21268 and dP[Tyr(Me)(2)]AVP. These results suggest that intracerebroventricular leptin administration activates the HPA axis by AVP receptor activation through V(1a) receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.
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PMID:Centrally administered murine-leptin stimulates the hypothalamus-pituitary- adrenal axis through arginine-vasopressin. 1087 98

States of increased metabolic demand such as fasting modulate hypothalamic neuropeptide gene expression and decrease circulating leptin levels. This study tested the hypotheses that fasting stimulates gene induction mediated by cAMP response element (CRE)-dependent increases in gene transcription and that fasting-induced decreases in leptin can regulate this CRE-mediated gene induction. Using C57BL/6J mice transgenic for a CRE-lacZ construct, an immunocytochemical study showed that fasting activated reporter gene expression in the hypothalamic arcuate nucleus (Arc) in a small subset of neurons and increased phosphorylation of CRE binding protein. The increase of beta-galactosidase expression caused by fasting was inhibited by a protein kinase A inhibitor, Rp-8-Br-cAMPS, when the compound was microinjected into the medial basal hypothalamus, and enhanced by intraperitoneal injection of selective phosphodiesterase inhibitors. In situ hybridization studies showed that neuropeptide Y (NPY) mRNA levels increased in the Arc during fasting, whereas proopiomelanocortin (POMC) mRNA levels decreased. Double labeling of mRNA and beta-galactosidase immunoreactivity in the fasted brain indicated that the subpopulation of the neurons expressing beta-galactosidase all produced NPY but not POMC. To study the possible involvement of decreased circulating leptin during starvation on CRE-mediated gene induction, leptin was administered intraperitoneally to fasted mice. Leptin significantly attenuated both beta-galactosidase expression and NPY gene expression stimulated by fasting, suggesting that leptin inhibits fasting-stimulated NPY gene expression at least in part through downregulation of CRE-mediated gene induction in the Arc. Leptin-induced modification of CRE-mediated gene induction in the Arc may play an essential role in the central regulation of feeding behavior and energy expenditure.
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PMID:Downregulation of fasting-induced cAMP response element-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus. 1116 Mar 94

We have shown in a previous study that high corticosterone levels during repeated immobilization stress result in a reduction of glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus (PVN) and the hippocampus. The reduction of GR presumably accounts for loss of or decrease in glucocorticoid-negative feedback, and thus hyperfunction of the hypothalamic-pituitary-adrenocortical (HPA) axis persists during chronic stress. Starvation is a stress state in which the counterregulatory responses against the loss of food occur in the central nervous system. We explored the impact of starvation on the HPA axis, GR and mineralocorticoid receptor (MR) mRNAs in the hippocampus, the PVN, and the anterior pituitary (AP) of rats. Rats were starved for 4 days and sacrificed in the morning. Starved rats showed high levels of plasma corticosterone, whereas neither plasma corticotropin (ACTH), AP proopiomelanocortin (POMC) mRNA nor AP type-1 corticotropin-releasing hormone (CRH) receptor mRNA was altered in the starved rats. In the presence of high corticosterone, starvation resulted in a decrease in both CRH mRNA and type-1 CRH receptor mRNA in the PVN. Consistently, the starved rats did not show any changes in GR mRNA in the hippocampus (CA1-2, CA3, and dentate gyrus), the PVN or the AP despite the elevation of plasma corticosterone. A significant decrease in MR mRNA was seen in the dentate gyrus and the AP, but not in CA1-2, CA3 or PVN. The lack of reduction of GR may be one of the organism's counterregulatory responses during starvation, which allows an intact glucocorticoid negative feedback, thereby resulting in decreased anorectic neuropeptide levels, namely CRH, in the PVN. The results also indicate that GR mRNA in the hippocampus and other brain regions is not solely regulated by circulating glucocorticoids. The mechanism underlying the regulation of GR mRNA in the central nervous system remains to be clarified.
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PMID:Lack of decrease in hypothalamic and hippocampal glucocorticoid receptor mRNA during starvation. 1147 19

During starvation, counterregulatory responses to loss of food (i.e. responses that lead to an increase in appetite) occur in the central nervous system (CNS). This study was designed to examine whether middle-aged rats show greater or smaller behavioural, peripheral and central hormonal responses during starvation compared to young rats. In experiment 1, refeeding following 4 days of starvation was measured in both middle-aged (72-week-old) and young (9-week-old) rats. The level of refeeding was similar to each prestarved level until 3 days after the end of starvation in both groups. From the 4th day, the level of refeeding in young rats increased and reached beyond the prestarved level, whereas refeeding in middle-aged rats remained similar to the prestarved level. Thus, overall refeeding throughout 7 days was greater in young rats than in middle-aged rats. In experiment 2, middle-aged and young rats were starved for 4 days and were killed in the morning. Middle-aged rats showed a smaller plasma corticosterone response than that of young rats. The magnitude of decreases in plasma glucose, insulin and leptin was similar in both groups. In the arcuate nucleus, the starvation-induced increase in neuropeptide Y (NPY) mRNA and the decrease in proopiomelanocortin (POMC) mRNA were smaller in middle-aged rats than in young rats. In contrast, the starvation-induced decrease in corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus was greater in middle-aged rats than young rats. The magnitude of decrease in type-2 CRH receptor mRNA in the ventromedial hypothalamus was similar in both groups. The results indicate that (a) ageing impaired refeeding response (b), middle-aged rats showed the same directional neuropeptide mRNA responses as seen in young rats during starvation and (c) the magnitude of these counterregulatory responses in the CNS in middle-aged versus young rats was not uniform, but rather was site-specific or neuropeptide-specific. This study suggests the importance of NPY and POMC responsiveness in the arcuate nucleus in the age-related differences resulting from starvation-induced refeeding.
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PMID:Differential neuropeptide responses to starvation with ageing. 1172 3

Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by alpha-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp(-/-)) mice to examine the physiological role of AgRP. Agrp(-/-) mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp(-/-) mice display normal responses to starvation, diet-induced obesity, and the administration of exogenous leptin or neuropeptide Y (NPY). In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin, Mc3r, Mc4r, or NPY mRNAs in Agrp(-/-) mice. As AgRP and the orexigenic peptide NPY are coexpressed in neurons of the arcuate nucleus, we generated AgRP and NPY double-knockout (Agrp(-/-);Npy(-/-)) mice to determine whether NPY or AgRP plays a compensatory role in Agrp(-/-) or NPY-deficient (Npy(-/-)) mice, respectively. Similarly to mice deficient in either AgRP or NPY, Agrp(-/-);Npy(-/-) mice suffer no obvious feeding or body weight deficits and maintain a normal response to starvation. Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.
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PMID:Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. 1207 32

Data are reviewed that support the hypothesis that the neural control of energy expenditure is distributed among several brain sites. This view contrasts with that expressed most commonly in literature, that a single site-the arcuate hypothalamic nucleus-receives and integrates signals of relevance to energy status assessment and engages the effector circuits that orchestrate responses that maintain energy balance. The data reviewed support a contribution from medullary neurons, including those of the nucleus of the solitary tract, in the integration of signals of relevance to energy balance and in the issuing of commands to local behavioral and autonomic effectors. Experimental evidence is discussed that supports the following specific conclusions: hindbrain neurons integrate oral and gastrointestinal signals and issue commands to local motor circuits that control meal size; leptin's effect on food intake may be mediated, in part, by a direct action on the hindbrain neurons that respond to gastric distention; deprivation signals, such as the fall in leptin level, affect gene expression outside of the hypothalamus with reductions in proglucagon and proopiomelanocortin message seen in nucleus of the solitary tract-rich tissue; and that hindbrain neurons contribute to the control of energy expenditure seen with food deprivation and increases in expenditure after cold exposure or starvation. Future work is needed to define how the nucleus of the solitary tract and arcuate nodes of the central energy balance control network interact to collectively, or separately, influence specific aspects of energy balance control in the intact brain.
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PMID:Distributed neural control of energy balance: contributions from hindbrain and hypothalamus. 1702 70

Recent evidence demonstrated that posttranslational processing of neuropeptides is critical in the pathogenesis of obesity. Leptin or other physiological changes affects the biosynthesis and processing of many peptides hormones as well as the regulation of the family of prohormone convertases responsible for the maturation of these hormones. Regulation of energy balance by leptin involves regulation of several proneuropeptides such as proTRH and proopiomelanocortin. These proneuropeptide precursors require for their maturation proteolytic cleavage by the prohormone convertases 1 and 2 (PC1/3 and PC2). Because biosynthesis of mature peptides in response to leptin requires prohormone processing, it is hypothesized that leptin might regulate hypothalamic PC1/3 and PC2 expression, ultimately leading to coordinated processing of prohormones into mature peptides. Leptin has been shown to increase PC1/3 and PC2 promoter activities, and starvation of rats, leading to low serum leptin levels, resulted in a decrease in PC1/3 and PC2 gene and protein expression in the paraventricular and arcuate nucleus of the hypothalamus. Changes in nutritional status also changes proopiomelanocortin processing in the nucleus of the solitary tract, but this is not reversed by leptin. The PCs are also physiologically regulated by states of hyperthyroidism, hyperglycemia, inflammation, and suckling, and a recently discovered nescient helix-loop-helix-2 transcription factor is the first one to show an ability to regulate the transcription of PC1/3 and PC2. Therefore, the coupled regulation of proneuropeptide/processing enzymes may be a common process, by which cells generate more effective processing of prohormones into mature peptides.
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PMID:Regulation of prohormone convertases in hypothalamic neurons: implications for prothyrotropin-releasing hormone and proopiomelanocortin. 1758 72


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