Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions. 256 86

The effects of intracerebroventricular or intracarotid injection of synthetic rat calcitonin gene-related peptide (CGRP) on growth hormone (GH) secretion induced by various stimuli in male rats were examined. CGRP (2.5 or 5 micrograms/rat intracerebroventricularly, i.c.v.) was administered 10 min before beta-endorphin (0.5 microgram/rat i.c.v.) or morphine (1 mg/kg intracarotidly, i.a.) or clonidine (0.25 mg/kg i.a.) or GH-releasing hormone (GHRH1-40; 2 micrograms/kg i.a.). When injected peripherally, CGRP (10 micrograms/rat, i.a.) was administered 5 min before morphine or GHRH. To investigate the possible involvement of somatostatin (SRIF) in the inhibition of GH secretion by CGRP, the effect of the peptide on GHRH-induced GH release was also examined in rats with hypothalamic SRIF depletion obtained by pretreatment (4 h before) with cysteamine (300 mg/kg subcutaneously). Blood samples for hormone determination were drawn from freely moving rats at various times before and after drug treatment. The intracerebroventricular administration of CGRP (5 micrograms/rat) significantly inhibited GH secretion induced by all the stimuli used. In rats with SRIF depletion CGRP did not modify the stimulation of GH by GHRH. When CGRP was administered intracarotidly, even the dose of 10 micrograms/rat did not reduce the GH release induced by GHRH or morphine. The effects of intracerebroventricular CGRP on basal or beta-endorphin-induced prolactin release were also examined. When given intracerebroventricularly, the peptide did not modify prolactin secretion. The present results indicate that CGRP has a central inhibitory role in the control of GH secretion, probably through a stimulation of SRIF release.
 ...
PMID:Evidence of a central inhibition of growth hormone secretion by calcitonin gene-related peptide. 278 61

The purpose of this study was to compare the binding potency to opioid receptors of met-enkephalin-derived, hypophysiotrophic peptides with their reported growth hormone (GH)-releasing strengths in vitro and further, to determine the relative selectivity of each peptide for mu and delta opioid binding sites in the forebrain of the rat. A series of (GH)-releasing pentapeptides and hexapeptides (GHRP's), as well as rat (rGHRH) and human (hGHRH) growth hormone-releasing hormones were tested for preferential binding to specific opioid receptors. The site selectivity of each peptide was determined by its ability to compete for binding with synthetic ligands for mu (Tyr-D-Ala-Gly-MePhe-Gly-ol; DAGO) and delta ([D-Pen2,5]-enkephalin; DPDPE) opioid receptors. The various peptides differed in their selectivities for the two opioid receptors in that most of the GHRP's were mu-selective, while the naturally occurring GHRH's were delta-selective. Amidation of the C-terminal decreased delta selectivity. Besides affecting selectivity for the site, structural changes that enhanced GH-release by enkephalin-derived peptides also decreased their potency to compete for opioid binding sites. For example, dose-response curves for His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (SK&F 110679) inhibition of the binding of DAGO and DPDPE yielded IC50's of 6 and 20 microM, respectively. In contrast, Tyr-D-Trp-Gly-Phe-Met-NH2 (BI360), which is 1 X 10(3) times weaker than SK&F 110679 in releasing GH, had IC50's of 0.1 microM and 0.08 microM for inhibition of the binding of DAGO and DPDPE, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Binding of growth hormone-releasing hormones and enkephalin-derived growth hormone-releasing peptides to mu and delta opioid receptors in forebrain of rat. 285 11

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
 ...
PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

During the last few years, many neuropeptides have been isolated, characterized and synthesized. Neuroendocrinology is one area in which there has been major progress, particularly through the isolation of two new hypothalamic factors, corticotropin releasing factor (CRF) and growth hormone releasing factor (GRF). CRF specifically stimulates pituitary secretion of ACTH and other peptides derived from pro-opiomelanocortin (beta-lipotropin, beta-endorphin), while GRF, together with somatostatin, controls secretion of the growth hormone. Knowledge of the structures of the hypothalamic factors has allowed the synthesis of the native substances as well as many potent analogues with agonist and antagonist properties. These substances have numerous clinical applications. LHRH or its analogues are presently used or being tested in various conditions such as treatment of hormone-related cancers (prostate, breast), endometriosis, idiopathic precocious puberty as well as in sterility problems. The recent availability of long acting somatostatin analogues has raised great therapeutic expectations in various endocrine and digestive diseases. Whereas GRF can be used in the treatment of short stature, CRF has so far not been shown to be a potential important therapeutic agent. However, its clinical application as a diagnostic test is clearly useful in many situations. There is a promising future for the clinical applications of these substances in various endocrine, digestive and perhaps in psychiatric diseases, and in hormone-related cancers.
 ...
PMID:[Hypothalamic factors: recent diagnostic and therapeutic advances]. 289 Feb 1

We have examined the effects of human GH-releasing factor (1-44) (GRF), cortisol and somatostatin-(1-14) on GH gene expression in solid tissue and dispersed cells from human pituitary adenomas using quantitative in-situ hybridization histochemistry. Sections cut from tissue obtained at hypophysectomy from three acromegalic patients were hybridized to probes directed against mature alpha-subunit, GH, prolactin, pro-opiomelanocortin, TSH beta-subunit and LH beta-subunit mRNA. Only one biopsy contained GH mRNA in isolation. A second was found to coexhibit GH, prolactin and alpha-subunit mRNA, and a third was found to contain prolactin, TSH beta-subunit, alpha-subunit and LH beta-subunit mRNA, with GH mRNA below the limit of specific detection, indicating that the sample was composed of normal rather than adenomatous pituitary tissue. GH mRNA in individual dispersed cells derived from the latter declined to barely detectable levels over 287 h, both in cultures containing GRF (10 ng/ml) or GRF (10 ng/ml) plus somatostatin (10 ng/ml) and in controls, but increased fourfold in cultures containing GRF (10 ng/ml) plus cortisol (0.5 mumol/l). GH mRNA remained unchanged in both adenoma samples over 138 and 450 h, irrespective of the addition of GRF or GRF plus hydrocortisone. In these samples, somatostatin plus GRF had no consistent effect. These studies confirm that quantitative in-situ hybridization histochemistry can be used to investigate hormone gene regulation in small samples of human tissue and should enable us to define more clearly the level at which abnormal gene regulation occurs.
 ...
PMID:Quantitative in-situ hybridization histochemistry studies on growth hormone (GH) gene expression in acromegalic somatotrophs: effects of somatostatin, GH-releasing factor and cortisol. 290 68

A human GRF 1-37 antiserum demonstrates a new neuronal system in lateral perifornical areas of the human hypothalamus. The molecule that is revealed in those neurons cannot be somatocrinin. Perikarya are abundant. They are observed beginning with the 9th week of development. alpha-MSH-like immunoreactivity, which is showed in the analogous cells of the rat, is not yet established in human. The early differentiation of those neurons and their abundance during the fetal life attest to the important neurophysiological function of the unidentified peptide they secrete.
 ...
PMID:[Ontogenesis in man, of a population of neurons in the dorsal and lateral hypothalamus, secretors of a peptide that has not yet been characterized]. 294 64

Pregnant rats were injected with saline or L-tyrosine methylester HCl (200 mg/kg) and subjected to an acute forced immobilization stress on day 20 of gestation. At 10, 30, 60, and 120 minutes after the onset of stress, their fetuses were dissected out, and the contents of hypothalamic and pituitary immunoreactive beta-endorphin (IR-beta-EP) and hypothalamic immunoreactive growth hormone-releasing factor (IR-GRF) were determined by specific radioimmunoassays. The maternal stress arose a significant decrease of hypothalamic IR-beta-EP at 30 minutes, while pituitary IR-beta-EP slightly elevated at 30 minutes, then declined at 60 minutes. Hypothalamic IR-GRF showed a gradual increase during the maternal stress. Tyrosine supplementation tended to attenuate stress-induced changes in hypothalamic and pituitary IR-beta-EP, but the response of hypothalamic IR-GRF was less modified by tyrosine. These results showed the functional changes in fetal central beta-EP and GRF under maternal stress in the late gestational life, and suggested that catecholaminergic regulations participate, at least in part, in the fetal neuroendocrine response to maternal stress.
 ...
PMID:The effect of an acute maternal stress on beta-endorphin and growth hormone releasing factor in the rat fetus. 296 92

Ovine corticotropin-releasing factor (oCRF) stimulates increased plasma immunoreactive adrenocorticotropin (IR-ACTH) and IR-cortisol at threshold, half-maximal, and maximal doses of 0.01-0.03, 0.3-1, and 3-10 micrograms/kg, respectively. Side effects occur with increasing frequency, severity, and duration at doses above 1 microgram/kg. oCRF has a prolonged duration of action, at least in part because of the long circulating half-life of intact oCRF in plasma. Increasing doses of oCRF given in late afternoon progressively diminish the next morning's circadian rise in plasma IR-ACTH in normal subjects, but not in Addisonian patients or subjects receiving metyrapone, indicating that prolonged oCRF-induced hypercortisolemia is the cause. Plasma IR-lipotropins and IR-beta-endorphin rise and fall concomitantly with IR-ACTH after oCRF injection. Arginine vasopressin increases the IR-ACTH response to oCRF fourfold when given simultaneously with oCRF. Cushing's disease patients respond variably, suggesting that oCRF may not be a very useful diagnostic agent in Cushing's syndrome. However, the combination of oCRF with growth hormone-releasing factor, gonadotropin-releasing hormone, and thyrotropin-releasing hormone appears to provide a rapid and useful test of combined anterior pituitary function.
 ...
PMID:Clinical studies with synthetic ovine corticotropin-releasing factor. 298 41

Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human pancreatic tumor GH-releasing factor. 298 23


<< Previous 1 2 3 4 5 6 7 8 Next >>