Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:040593 (CRH)
 2,662 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has examined the effects of insulin-induced hypoglycemia on expression of the CRH, arginine vasopressin, and POMC genes and corresponding peptides in freely moving, unanesthetized, male Sprague-Dawley rats. Animals were infused with 150 mM NaCl for 3 days before the experimental day and were then administered insulin (4 U/kg) or saline iv. In one experiment animals were killed 0, 30, 60, or 90 min after insulin or saline, and RNA was isolated from anterior pituitary, cerebral cortex, and punches of the hypothalamic paraventricular and supraoptic nuclei. In a second experiment, animals were killed 90 min after insulin or saline treatment, and RNA was isolated from whole hypothalami. RNA was analyzed by Northern blot. Plasma glucose fell from 106 +/- 5 to 38 +/- 2 mg/dl after insulin administration and remained low for the duration of the experiment. Plasma levels of ACTH, corticosterone, and vasopressin were 10-, 6-, and 4-fold higher, respectively, in the insulin-treated vs. control animals (by analysis of variance, P less than 0.0001 in all cases), while plasma CRH was unchanged. During hypoglycemia POMC mRNA levels were 1.8-fold higher in the insulin-treated group (by analysis of variance, P less than 0.025). In contrast, paraventricular nucleus, whole hypothalamic, and parietal cortex CRH mRNA and vasopressin mRNA were unchanged. These data support previous studies which indicated that POMC gene expression is increased by hypoglycemia. However, we found no evidence for an increase in paraventricular nucleus or cerebral cortex CRH mRNA expression during hypoglycemia-associated stimulation of the hypothalamic-pituitary-adrenal axis, suggesting that another factor(s) may mediate the observed increase in POMC gene expression.
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PMID:The effect of insulin-induced hypoglycemia on gene expression in the hypothalamic-pituitary-adrenal axis of the rat. 131 Feb 84

To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 microgram/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d-FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 microgram/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 +/- 11.2 ng/mL v 104.1 +/- 9.5 ng/mL). This response was lower (P less than .005) than in the controls, in whom the basal cortisol value of 120.6 +/- 11.8 ng/mL reached a peak value of 221.2 +/- 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P less than .0001) plasma cortisol (peak value 170.6 +/- 18.0 ng/mL v 111.5 +/- 10.8 ng/mL) and the response was enhanced (P less than .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 +/- 1.7 pg/mL v 9.6 +/- 1.1 pg/mL), but the hormonal response was lower (P less than .005) than in controls (peak value 38.1 +/- 5.5 pg/mL v 13.8 +/- 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P less than .05) in plasma ACTH at 30 minutes (20.4 +/- 3.7 pg/mL v 10.9 +/- 0.9 pg/mL) and 45 minutes (18.0 +/- 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects. 131 2

To study the cellular mechanisms of interleukin-1 (IL-1) in the pituitary corticotroph, we studied the properties of IL-1 receptors on a mouse pituitary ACTH-producing cell line, AtT-20. Scatchard plot analysis revealed a single type of receptor with a Kd (dissociation constant) of 93 pM, and 482 binding sites/cell. [125I]IL-1 alpha binding competed with IL-1 alpha and IL-1 beta in an equimolar fashion. A 24 h pre-incubation with either CRH, epinephrine or nor-epinephrine increased the [125I]IL-1 alpha binding sites in the AtT-20 cells and conversely, a similar pre-incubation with either dexamethasone or tumour necrosis factor-alpha (TNF alpha) decreased them without affecting the affinity of the receptors in either case.
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PMID:Regulation of interleukin-1 receptors on AtT-20 mouse pituitary tumour cells. 131 14

Hypothalamic CRH is the primary positive regulatory factor of the pituitary-adrenal axis. The purpose of our study was to analyze the chronic effects of CRH on the production and secretion of POMC peptides from both the anterior lobe (AL) and neurointermediate lobe (NIL) of the pituitary by mimicking the syndrome of ectopic CRH secretion from neuroendocrine tumors. We first generated stably transfected W2 medullary thyroid carcinoma cell lines with a rat CRH expression vector under the transcriptional control of a cytomegalovirus gene promoter. These cell lines constitutively expressed the foreign gene, accurately processed the encoded prepro-CRH, and secreted biologically active CRH with an estimated potency equivalent to that of synthetic CRH-(1-41)NH2. The cell line designated W2CRH-7 was implanted sc in the syngeneic rat strain WAG/Rij and produced tumors that abundantly secreted CRH into the peripheral circulation. Four weeks postimplantation, W2CRH-7, but not wild-type W2, cells caused significant increases in the AL content of beta-endorphin-like immunoreactivity comparable to that caused by adrenalectomy (ADX). Plasma ACTH and serum beta-endorphin-like immunoreactivity were increased to a greater extent by ADX than by W2CRH-7 cell implantation. The NIL of both male and female rats showed either no change or a tendency to decreased beta-endorphin concentrations with no change in the acetylation or carboxy-shortening profiles judged by cation exchange chromatography in response to the ectopic CRH treatment. Rats of both sexes maintained a profound activation of the pituitary adrenal axis up to 16 weeks postimplantation, with normalized adrenal gland weights 5 times that of controls. The chronic secretion of CRH by W2CRH-7 cells resulted in a complete cessation of body growth in all rats up to the maximum time tested of 16 weeks. The lack of growth was partly ameliorated by concomitant ADX, suggesting an important role for adrenal glucocorticoids in these effects. We conclude that 1) the transplantable W2CRH-7 cell line provides a highly effective and reproducible means of sustained CRH treatment that mimics the syndrome of ectopic CRH expression by neuroendocrine tumors; 2) AL corticotrophs respond to chronic CRH by a sustained production and secretion of POMC peptides, leading to a marked adrenal cortical hyperplasia, with no evidence of biologically significant desensitization; 3) chronic CRH tends to decrease the NIL content of beta-endorphin,with remarkably little effect on posttranslational processing; and 4) the syndrome of chronic ectopic CRH in WAG/Rij rats includes a cessation of body growth at least partly due to products of the adrenal glands.
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PMID:Ectopic corticotropin-releasing hormone produced by a transfected cell line chronically activates the pituitary-adrenal axis in transkaryotic rats. 131 32

A 42-year-old man and a 51-year-old woman with a positive history of weakness and gastrointestinal complaints were shown to have low basal plasma cortisol and ACTH levels, and low daily urinary excretion of free cortisol. An empty sella was found in patient no. 1, while patient no. 2 was hypothyroid. Both patients showed a normal plasma cortisol response to ACTH and an increment in plasma ACTH and lipotropin levels after ovine CRH (oCRH), lysine vasopressin (LVP) and oCRH-LVP stimulation tests. These studies clearly report an isolated idiopathic ACTH deficiency due to a deficit in CRH in two adult subjects.
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PMID:Isolated adrenocorticotropic hormone deficiency secondary to hypothalamic deficit of corticotropin releasing hormone. 131 44

The functional role of neuropeptide receptors in the immune system seems to be sensory and regulatory. Signaling molecules (i.e. neuropeptides/neurotransmitters) secreted by immune or neuroendocrine cells can interact with specificity to immunocyte membrane bound neuroendocrine peptide receptors resulting in changes in immune homeostasis. At the onset of this review, three criteria were established in order to formally define the existence of a receptor including the pharmacologic, biochemical, and biological profiles. Applying these criteria, at least ten neuroendocrine peptide/peptide neurotransmitter receptors have met the requirements (table 1). Perhaps more striking, many of these receptors have characteristics which are nearly identical to those receptors found on neuroendocrine tissue. This observation implies irregularities in the physiology of a receptor system in one tissue compartment (neuroendocrine or immune) may be mirrored by the receptors found in the other compartment (neuroendocrine or immune) as well. This rather hypothetical concept is, in fact, supported by data studying ACTH, CRH, and TRH receptors on immune cells relative to the expression or function of these receptors in neuroendocrine tissue taken from patients with neuroendocrine disorders. It is likely that future work will use this relationship to further study the dynamic interaction between the immune and neuroendocrine systems in defining neurologic, neuroendocrine, and autoimmune disorders.
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PMID:Neuroendocrine peptide receptors on cells of the immune system. 131 10

To characterize the recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term glucocorticoid treatment, we examined the responses to ovine CRH (oCRH) before and after prednisolone administration. Eight normal male volunteers were studied before (control) and after administration of 25 mg prednisolone twice daily orally for 14 days. Data are mean +/- SEM. The ACTH basal level was suppressed 24 h after prednisolone withdrawal (1.7 +/- 0.4 pmol/L vs. control, 3.5 +/- 0.6, P less than 0.02), but the ACTH response to oCRH was not significantly different from control (peak 12.8 +/- 2.0 pmol/L vs. 13.5 +/- 12.1, respectively). Seventy-two h post prednisolone basal ACTH levels had recovered to pretreatment values. Cortisol levels, both basal and in response to oCRH, were significantly suppressed 24 h post prednisolone (P less than 0.001). By 72 h post prednisolone, both basal and oCRH-stimulated cortisol had recovered to pretreatment levels. Dehydroepiandrosterone (DHEA), both basal and stimulated, was significantly suppressed 24 h post prednisolone (P less than 0.001). In contrast to cortisol, basal and peak DHEA remained suppressed 72 h post prednisolone (basal DHEA 9.1 +/- 1.1 nmol/L, P less than 0.05 vs. control; peak DHEA 20.0 +/- 3.3 nmol/L, P less than 0.01 vs. control). When expressed as percent rise, however, the DHEA response to oCRH was not significantly different from control. DHEA sulfate (DHEAS) was significantly lower than control at both 24 and 72 h post prednisolone (1.8 +/- 0.3 and 3.3 +/- 0.4 mumol/L respectively; control 7.2 +/- 0.7 mumol/L; P less than 0.001). The ratio of basal DHEA to DHEAS was significantly higher than control 72 h post prednisolone, indicating that DHEAS was more profoundly suppressed than DHEA. We conclude that after a short course of prednisolone pituitary ACTH secretion is the first parameter of the hypothalamic-pituitary-adrenal axis to recover. Hypothalamic secretion of CRH recovers next, followed by recovery of cortisol secretion. Secretion of DHEA and DHEAS remain suppressed after recovery of cortisol. This suppression may be caused by inhibition of sulfokinase activity by glucocorticoid.
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PMID:Recovery of responses to ovine corticotropin-releasing hormone after withdrawal of a short course of glucocorticoid. 131 44

Gastrin-releasing peptide (GRP; mammalian bombesin) may be involved in the neuroendocrine regulation of pituitary hormone secretion. We investigated the effect of GRP on ACTH secretion in conscious male rats. GRP (7-700 pmol) stimulated ACTH secretion dose-dependently after intracerebroventricular (icv) administration but had no effect after iv administration. GRP infused icv in a dose of 7 pmol, which alone increased ACTH 1.5-fold, potentiated the ACTH-releasing effect of arginine vasopressin (AVP; 80 pmol iv) and corticotropin-releasing hormone (CRH; 100 pmol iv). A higher dose of GRP (70 pmol icv), which stimulated ACTH secretion 2-fold, potentiated the effect of 80 and 400 pmol AVP iv, but had only additive effect on the ACTH response to 800 pmol AVP iv or 100 pmol CRH iv. GRP infused iv in a dose of 210 pmol, which in itself had no effect on ACTH secretion, potentiated the ACTH-stimulating effect of AVP and CRH approximately 2.5-fold. The effect of GRP (icv or iv) on AVP or CRH-stimulated ACTH release was only slightly smaller than the effect of combined administration of AVP and CRH (80 + 100 pmol iv). The ACTH-stimulating effect of GRP (700 pmol icv) was inhibited about 60% by pretreatment with either CRH or AVP antiserum and prevented by combined pretreatment with the antisera. The results indicate that: 1) GRP affects ACTH secretion indirectly at a suprapituitary level--possibly in the hypothalamus--by stimulating the release of AVP and CRH to the pituitary portal blood; and 2) GRP acts directly at the pituitary level to augment the effect of AVP and CRH on the corticotrophs. We suggest that GRP is involved in the multifactorial regulation of ACTH secretion.
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PMID:Gastrin-releasing peptide stimulation of corticotropin secretion in male rats. 131 54

The objective of this study was to determine if there are age-related alterations in hemodynamic and/or neuroendocrine responses to the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly(ol)5] enkephalin (DAMGO), or corticotropin releasing hormone (CRH) administered centrally. To this end, DAMGO (1-3 nmoles) or CRH (1 nmole) was injected intracerebroventricularly (icv) to freely moving young (6-8 month) and aged (24-26 month) Fischer 344 male rats. Blood pressure, heart rate (HR), and plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropin (ACTH), and prolactin (PRL) were measured over time. Under basal conditions, NE levels were higher and blood pressures were lower in aged rats, whereas there were no significant differences in EPI, ACTH, or PRL levels. The stimulatory effect of DAMGO on blood pressure, HR, and plasma EPI and ACTH was attenuated, but the PRL response was enhanced in aged cohorts. In contrast, there were no age-related differences in the NE responses to DAMGO or CRH nor in CRH-induced increases in EPI or ACTH. The sympathoadrenal and hemodynamic effects of DAMGO were blocked by naloxone in both age groups. These results indicate that alterations in mu-opioid function with age are specific for the opioid system and do not reflect a generalized decline in central regulation of neuroendocrine and cardiovascular function.
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PMID:Selective impairment of neuroendocrine and hemodynamic responses to a mu-opioid peptide in aged rats. 131 52

CRH, a hypothalamic peptide that is the most potent ACTH secretagogue known, also appears to be produced in the cerebral cortex and spinal cord. Depressed patients have blunted responses to exogenous CRH and normal to high concentrations of CRH immunoreactivity in single morning samples of lumbar cerebrospinal fluid (CSF). Although these data suggest that depression may be associated with hypersecretion of CRH, it has also been postulated that central nervous system insufficiency of CRH might have a pathophysiological role in certain depressive syndromes. We continuously sampled lumbar CSF via indwelling subarachnoid catheters from 1100-1700 h and measured CRH at 10-min intervals in depressed patients and normal subjects. A standardized mixed liquid meal was administered at 1300 h. CSF CRH was strikingly reduced in depressed patients compared to normal subjects [4.2 +/- 1.1 pmol/L vs. 13 +/- 2.1 pmol/L (mean +/- SEM), respectively, P less than 0.01 by Wilcoxon test]. CSF CRH concentrations rose progressively during the experiment in both groups, suggesting a diurnal rhythm and, possibly, response to a test meal. CRH had a very brief half-life in CSF (less than 10 min), suggesting that the spinal cord is the origin of CRH in lumbar CSF. The rapid transients in CSF CRH concentration demonstrate that single samples provide very limited information. There were no intraindividual correlations between CSF CRH concentrations and those of either plasma ACTH or cortisol, both of which rose in response to eating. The present data show that impaired central nervous system secretion of CRH can exist during states of severe depression.
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PMID:Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed humans. 131 85


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