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

Complementary oligonucleotide probes specific for the human pro-opiomelanocortin (POMC) mRNA were used to analyze the expression of POMC gene in 56 human postmortem pituitaries by in situ hybridization histochemistry. POMC transcripts were visualized by autoradiography in anterior lobe of the pituitary where their distribution was in a 'patchy-like' pattern. No hybridization could be observed in the posterior lobe of the pituitary. We examined pituitaries from several controls and from patients dying with schizophrenia, Parkinson's disease. Alzheimer's disease, Wernicke's encephalopathy and depressive illness. Computer-assisted microdensitometric semiquantification of POMC mRNA using a complementary oligonucleotide as hybridization standard, revealed no statistically significant effect of postmortem delay (between 2.5 and 66 h), of gender, age (between 22 and 103) or cause of death in 56 human pituitary glands. A large variation in POMC levels was already observed among all 30 control cases. The levels of POMC mRNA observed in pituitaries from different pathologies did not show a significant variation when compared with control cases.
Brain Res Mol Brain Res 1991 May
PMID:Study of pro-opiomelanocortin mRNA expression in human postmortem pituitaries. 171 87

It has been postulated that some endocrine responses to stressful stimuli are mediated through the activation of hypothalamic pro-opiomelanocortin (POMC)-derived peptides. The aim of the present study was to analyse the effect of chronic stress on expression of the POMC gene in the medial basal hypothalamus and pituitary, and on serum concentrations of LH, beta-endorphin and corticosterone. Adult male rats were killed after being subjected to restraint stress for 6 h/day over 2, 3 or 4 days. Chronic restraint induced an increase in serum concentrations of beta-endorphin and corticosterone and a decrease in serum LH levels. To determine whether chronic stress induced any change in POMC synthesis, a dot-blot method was used to measure POMC mRNA levels. No significant changes were detected either in the beta-endorphin content or in POMC mRNA levels in the medial basal hypothalamus after 2, 3 or 4 days of chronic restraint. This observation contrasts with the stimulation of POMC mRNA levels in both lobes of the pituitary. The data suggest that although chronic restraint induces an increase in POMC synthesis and secretion in the pituitary and a decrease in LH secretion, it has no effect on hypothalamic POMC neurones.
J Mol Endocrinol 1991 Dec
PMID:Influence of chronic restraint stress on pro-opiomelanocortin mRNA and beta-endorphin in the rat hypothalamus. 177 41

Proopiomelanocortin (POMC) is a polyprotein which is targeted to the regulated secretory pathway of neuroendocrine cells where it undergoes tissue-specific proteolysis to yield peptides such as adrenocorticotropic hormone, beta-lipotropin and beta-endorphin. The pro-region of POMC is 49 amino acid long with two disulfide bonds between cysteine residues 2 and 24 and 8 and 20. These cysteine residues are conserved across the species. The pro-region contains no known hormonal sequence. Sorting to the regulated secretory pathway is thought to involve targeting signals encoded in the structure of secretory proteins. In the present study, we have examined the possibility that the disulfide bridges located in the NH2-terminal portion of the pro-region of POMC are essential for maintaining a determinant involved in the sorting of POMC to the regulated secretory pathway. Using site-directed and deletion mutagenesis of the porcine POMC cDNA, we created mutants in which one or both disulfide bridges were disrupted or in which the first 26 amino acid residues of the pro-region were deleted. Recombinant retroviruses carrying the mutated POMC cDNAs were used to infect Neuro2A cells. Immunofluorescence and immunoelectron microscopy studies performed on infected cells revealed that the unmutated and mutated POMC-immunoreactive peptides were localized in dense-core vesicles at the tips of cellular extensions. Analysis of the POMC-immunoreactive peptides extracted from the infected Neuro2A cells indicated that the mutated precursors in which one disulfide bridge was disrupted (POMC-S2 or POMC-S8) were stored and processed as efficiently as the unmutated POMC. By contrast, the mutated precursor in which both disulfide bridges were disrupted (POMC-S2,8) did not accumulate in intracellular compartments to the same extent as unmutated POMC. Moreover, this mutant was very inefficiently processed and no release could be observed upon stimulation of the cells with K+/Ca2+. These results suggest that POMC-S2,8 entered the regulated secretory pathway less efficiently than the unmutated precursor. However, when both disulfide bridges were removed from the precursor from the precursor by deletion of the first 26 amino acid residues of POMC, the truncated precursor (POMC delta 1-26) behaved as the unmutated POMC. Taken together our results indicate that the NH2-terminal portion of the pro-region including both disulfide bridges can be deleted without affecting the targeting of the molecule to secretory granules. However, when the entire POMC sequence is expressed in Neuro2A cells, the proper folding of the NH2-terminal region might be important for efficient processing and targeting.
Mol Cell Endocrinol 1991 Dec
PMID:Investigation of a possible role of the amino-terminal pro-region of proopiomelanocortin in its processing and targeting to secretory granules. 179 12

The direct effects of hydrocortisone (HS) and adrenocorticotropin (ACTH) on testicular testosterone production were studied in purified immature pig Leydig cells in vitro. Leydig cells were obtained from 3- to 4-week-old piglet testes by enzymatical dispersion followed by discontinuous Percoll gradient centrifugation. Leydig cells were treated with HS and ACTH in the absence or presence of luteinizing hormone (LH) after 12 h of incubation. Media were collected 48 h later for testosterone and cyclic adenosine 3',5'-monophosphate (cAMP) measurement. Treatment of Leydig cells with increasing concentrations (0.001-10.0 micrograms/ml) of HS for 48 h resulted in a dose-dependent increase in basal and LH-stimulated testosterone production. Increasing duration (6-72 h) of treatment with HS (100 ng/ml) led to a time-dependent increase in basal and LH-stimulated testosterone production, achieving statistical significance by 48 and 24 h, respectively. HS increased LH-stimulated cAMP production. HS also increased testosterone production induced by (Bu)2 cAMP. Forskolin stimulated testosterone production to an extent comparable to that attained with LH, and HS augmented forskolin-stimulated testosterone production. HS enhanced the conversion of exogenous 17 alpha-hydroxyprogesterone to testosterone, but did not affect the conversion of pregnenolone and progesterone to testosterone, suggesting a specific stimulation of 17,20-desmolase. Porcine ACTH had no influence on basal and LH-stimulated testosterone production. These results suggest that HS directly stimulates immature pig Leydig cell steroidogenesis, at least in part via an enhancement of the generation of cAMP, leading to an increase in the activity of 17,20-desmolase.
J Steroid Biochem Mol Biol 1991 Feb
PMID:Effect of cortisol on testosterone production by immature pig Leydig cells. 184 43

Using in situ hybridization and immunohistochemistry, we have studied mRNA and peptide levels in the hypothalamic paraventricular nucleus (PVN) 24 h after a single large dose of reserpine (10 mg/kg, i.p.) and 24 h after an intraventricular (i.c.v.) injection of colchicine (120 microliters/20 microliters saline). Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for corticotropin-releasing hormone (CRH), neurotensin (NT), enkephalin (ENK), vasoactive intestinal polypeptide (VIP) and thyrotropin-releasing hormone (TRH). For immunohistochemistry rabbit antisera to CRH, NT, ENK, VIP and TRH were used. In situ hybridization showed a clear increase in CRH mRNA as compared to control rats after both treatments. Also NT and VIP mRNA could be seen in parvocellular neurons in reserpine and in colchicine-treated rats, whereas we so far have not been able to demonstrate these mRNAs in untreated rats. No changes in TRH mRNA could be detected after reserpine of colchicine. These results provide final evidence that subpopulations of parvocellular PVN neurons can synthesize not only CRH and ENK, but also NT and VIP, in agreement with earlier immunohistochemical results. With immunochemistry, after reserpine, many CRH-, but no NT- or VIP- positive neurons could be observed in the parvoecellular part of the PVN. The present results demonstrate that treatment with two drugs, the monoamine depleting drug reserpine and the mitosis inhibitor colchicine, causes increased levels of mRNA for several peptides in neurons of the PVN, located almost exclusively in its parvocellular part and being part of the hypothalamo-pituitary adrenal axis.
Brain Res Mol Brain Res 1991 Jan
PMID:Effect of reserpine and colchicine on neuropeptide mRNA levels in the rat hypothalamic paraventricular nucleus. 185 78

Arginine vasopressin (AVP) and beta-endorphin are present within the testis where they could act as paracrine effectors of steroidogenesis. In this study we investigated the effect of naloxone, an opioid receptor antagonist on Leydig cell AVP receptor. Intratesticular injection of increasing doses of naloxone (0.1-100 micrograms) resulted 24 h later in a dose-dependent increase in Leydig cell AVP binding capacity. This effect occurred locally since s.c. injection of similar doses of naloxone did not alter the testicular AVP receptor content and intratesticular injection enhanced AVP receptor density only in the naloxone-treated testis but not in the contralateral vehicle-treated testis. Scatchard plot analysis of the data revealed that naloxone locally injected altered AVP binding capacity without change in affinity. These results suggest that in addition to their known paracrine effects in the testis, endogenous opioid peptides may locally control the testicular AVP system by modulating AVP receptor capacity.
Mol Cell Endocrinol 1991 Aug
PMID:Local control of Leydig cell arginine vasopressin receptor by naloxone. 193 35

Pro-opiomelanocortin (POMC) is the precursor to several pituitary hormones and neuropeptides including adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-END). In neuroendocrine cells, peptide hormones and neuropeptides are targeted to the dense-core vesicles of the regulated secretory pathway. These vesicles are transported to the ends of cellular extensions where they are stored until they release their content upon external stimulation of the cell. In order to study the cellular mechanisms involved in targeting of neuropeptides, we have expressed POMC in Neuro2A cells, a cell line of neural origin. Using immunofluorescence labeling and immunoelectron microscopy we show that in Neuro2A cells POMC is packaged in dense-core vesicles which accumulate at the tips of cellular processes. Intracellular accumulation of POMC was not observed in NIH 3T3 fibroblasts. When a soluble form of an integral membrane protein, neutral endopeptidase (E.C. 3.4.24.11) (secNEP), was expressed in Neuro2A cells, the protein was found to be constitutively secreted without prior accumulation in dense-core vesicles. Our results suggest that in Neuro2A cells, targeting to the regulated secretory pathway is restricted to peptide hormones and neuropeptides and establish this cell line as a valid model for studying the molecular events involved in neuropeptide sorting into the regulated secretory pathway.
Mol Cell Endocrinol 1991 Aug
PMID:Expression of porcine pro-opiomelanocortin in mouse neuroblastoma (Neuro2A) cells: targeting of the foreign neuropeptide to dense-core vesicles. 193 37

The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids.
J Steroid Biochem Mol Biol 1991
PMID:Stress induced changes in testis function. 195 48

The molecular pathology of steroid 21-hydroxylase deficiency is attributable to unequal crossover-mediated gene deletion or to large- or small-scale replacement of the functional CYP21B gene sequence by a copy of the analogous CYP21A pseudogene sequence. Because the pathological point mutations originate from the pseudogene which shows only a small number of differences from the functional CYP21B gene sequence, the total number of different pathological point mutations is likely to be small. Mutant P450c21 enzymes carrying specific amino acid substitutions seen in patients with 21-hydroxylase deficiency exhibit activities that correlate with the clinical severity of the disease and with biochemical abnormalities such as 17-hydroxyprogesterone levels after ACTH (corticotropin) stimulation.
J Steroid Biochem Mol Biol 1991
PMID:Molecular pathology of steroid 21-hydroxylase deficiency. 195 56

Adrenal cells from 2-6-month-old young rats (Y cells) and from 19-25-month-old aged male rats (O cells) were adapted to primary monolayer culture. The cultures of Y and O cells appeared to be primarily epithelial and rounded up in response to stimulation with adrenocorticotropic hormone (ACTH). The general morphology of O cells was comparable to that observed in Y cells except for the presence of lipofuscin-like granules, a cellular marker of aging, in O cells, but not in Y cells. ACTH-stimulated steroid production by O cells was 52% lower than that by Y cells. Exposure of intact young rats to hypoxia (0.5 atmosphere) for 21 days prior to sacrifice and culture resulted in a 122% increase of ACTH-stimulated adrenal steroidogenic activity in the cultured cells, but this effect was not observed in adrenal cells cultured from hypoxic aged rats. The results suggest that there is an age-related diminution in rat adrenal steroidogenic capacity in response to ACTH stimulation in culture derived from Y and O animals; hypoxic stress magnifies this difference.
Mol Cell Endocrinol 1990 Oct 01
PMID:Diminished adrenal steroidogenic activity in aging rats: new evidence from adrenal cells cultured from young and aged normal and hypoxic animals. 196 13


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