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)

Anterior pituitary corticotrophin cells secrete ACTH as part of a larger precursor molecule, pro-opiomelanocortin. Post-translational cleavage of this precursor yields three major peptides: ACTH, beta-LPH and N-POMC. Experiments both in vivo and in vitro suggest that N-POMC may act as a prohormone amplifier for ACTH-induced adrenal steroidogenesis and as regulator of adrenocortical cell growth. The secretion of POMC is under the control of CRF. These findings are discussed in relation to the pathophysiology of corticotrophinoma. The primary defect in this condition appears to reside at the level of the anterior pituitary cell and is readily amenable to treatment by trans-sphenoidal microsurgery. The estimation of plasma ACTH concentrations is proving useful in the monitoring of various clinical conditions including Addison's disease and congenital adrenal hyperplasia.
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PMID:The hypothalamic-pituitary-adrenal axis. 632 65

Anterior pituitary corticotropes increase in number after stimulation by adrenalectomy or corticotropin-releasing hormone (CRH). However, is this brought about by mitoses? Furthermore, as epidermal growth factor (EGF) is a potent secretagogue for corticotropes, is it also a mitogen? To address these questions, populations of corticotropes enriched to 88-97% by counterflow centrifugation were studied after growth in 0-10 nM CRH with and without 0.1-10 ng/ml EGF. Three types of assays were used to detect changes in mitotic cells or cell number. An enzyme immunoassay for bromodeoxyuridine uptake during DNA synthesis [bromodeoxyuridine (BrDU) uptake] detected a 3-fold increase in optical density readings in the presence of 0.5 nM CRH or EGF. Together the peptides increased the optical density to 4.8-fold basal levels. No further increases in BrDU uptake were seen with higher concentrations of CRH or EGF. Cytochemical detection of BrDU uptake by immunolabeled corticotropes showed BrDU in 18 +/- 2% of 3- to 5-day ACTH cells. In the presence of 0.5 nM CRH or 0.5 ng/ml EGF, this value increased to 37 +/- 3% or 34 +/- 2% of ACTH cells, respectively. Together CRH and EGF stimulated increases in mitotic activity so that 47 +/- 4% of the ACTH cells were labeled for BrDU after a 1-h exposure. Cell growth/cell death assays in 3-(4,5-dimethyltiazol-2-yl)2,5- diphenyl tetrazolium bromide were also used to detect changes in overall cell number or cell survival in the same groups of enriched corticotrope cultures. Both 0.5 nM CRH and 0.5 ng/ml EGF caused increases to 1.5- to 1.7-fold basal readings. However, higher concentrations did not stimulate increases in number, and their combined effects were not additive. These studies show that CRH and EGF can be mitogens for ACTH-bearing corticotropes, in a limited dose range. In a higher dose range, their differentiating effects may eliminate dividing cells and retard further growth of the population.
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PMID:Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. 789 69

By using the primary culture method for pituitary cells in CSFM established in our laboratory, we studied the effects of lanthanum ion (La3+) on the biosynthesis and release of beta-endorphin-like immunoreactive substances in rat pituitary cells. Anterior and intermediate/posterior pituitary cells from male rats were cultured with arachidonic acid (AA), cortisol, dexamethasone (DEX) and lanthanum chloride. RIA was used to determine beta-EP levels in culture medium and within cells. The results indicated that AA could obviously stimulate the release of beta-EP from pituitary cells at a concentration of 2 x 10(-5) mol/L, while cortisol at 10(-6)mol/L and DEX at 10(-7)mol/L inhibited this release. These data coincide with results reported in the literature and thereby prove the reliability of the method used. When incubated with pituitary cells, lanthanum chloride induced a dose- and time-dependent release of beta-EP. Namely, beta-EP release continuously increased for a period under the action of La3+ of different doses (10(-5)mol/L and 10(-7)mol/L). beta-EP content in cells showed similar changes. These results suggest that beta-EP biosynthesis and release in rat anterior and intermediate/posterior pituitary cells are stimulated by lanthanum ions. They also provide experimental evidence for explaining the analgesic mechanism of lanthanum ions at the cellular level.
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PMID:[Effects of lanthanum ion on beta-endorphin biosynthesis and release in rat pituitary cells]. 795 66

The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA-producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region.
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PMID:Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression. 798 74

Thirty-six crossbred gilts (71.7 +/- .9 kg and 140.1 +/- .9 d) were assigned to one of three doses (0, 35, or 70 micrograms.kg BW-1 x d-1) of recombinant porcine somatotropin (rpST). The doses of rpST were adjusted weekly, and i.m. injections continued until d 50. Gilts were pen fed (six gilts/pen) a 17% CP corn-soybean diet (1.2% lysine and 3.2 Mcal of ME/kg). At d 50, feed intake, feed:gain ratios (P = .02), and blood urea nitrogen were decreased (P < .001) by increasing rpST doses, whereas ADG was increased (P = .04) by increasing rpST doses. Injections of rpST did not affect (P > .05) conception rate, age, or weight at puberty. Numbers of blastocysts or corpora lutea observed at d 10.4 +/- 1.5 of gestation (42.2 d after final rpST injection) were unaffected (P > .05) by rpST treatment. Anterior and posterior pituitary weights were increased (P < or = .003) linearly with rpST dose. However, liver, adrenal, and heart weights were unaffected (P > .05) by rpST. After a withdrawal period of 42.2 +/- 2.0 d, rpST increased (P < or = .02) the estimated percentage of lean by 5.8% and longissimus muscle area by 10.4%. Eighteen hours before the initial rpST injection (d 0), 10 gilts per rpST dose were catheterized. Catheterizations were repeated on d 40. The rpST or diluent was given i.m. in the extensor muscle of the neck 1 h after initiation of blood collection. Adrenocorticotropic hormone (1.4 IU/kg BW) was administered through the catheter 3 h after initiation of blood collection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of porcine somatotropin on endocrine and histological variables in gilts. 832 16

Anterior pituitary gland of the spontaneous dwarf rat (SDR) with isolated growth hormone (GH) deficiency was studied using immunocytochemistry, cell count and in situ hybridization. The standard immunocytochemistry of five anterior pituitary hormones [adrenocorticotropic hormone (ACTH), luteinizing hormone, thyroid-stimulating hormone, prolactin (PRL) and GH] and S-100 protein failed to detect any cytological difference between normal rats and SDRs, except for the size of different types of cells which were smaller in SDR than in normal rats, and GH cells which were undetectable in the SDR. The cell count study again showed lack of immunoreactive GH cells in the SDR. The population of PRL cells was significantly reduced in the SDR by 40% in male and 30% in female when compared to those of the control. The population of ACTH cells was larger in the male SDR. The population of the immunonegative cells was calculated by subtracting the sum of the percentages of immunopositive cells from 100, and it was found to be remarkably increased in the SDR. The population of immunonegative cells was about 55% in both male and female SDRs, whereas it was calculated to be 18.7% (male) or 10.2% (female) in the control rats. In situ hybridization study using GH cRNA indicated the presence of a considerable number of cells which express GH mRNA in the SDR as well as in the control rats. These results taken as a whole suggest the presence of a number of dysfunctional GH cells in the SDR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased population of nonhormone-producing cells suggests the presence of dysfunctional growth hormone cells in the anterior pituitary gland of the spontaneous dwarf rat. 838 99

Pituitary function was assessed in healthy adult beagle dogs before and after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consisted of sequential 30-sec intravenous injections of four hypothalamic releasing hormones, in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanotropin (alpha-MSH) response to the intravenous injection of the dopamine antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyroxine, LH. PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test and the haloperidol test, the peaks for the plasma concentrations of ACTH, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after injection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol responses, whereas in the other four dogs, plasma ACTH and cortisol responses were significantly attenuated. The basal plasma ACTH and cortisol concentrations were significantly lower in the corticotropic nonresponders than in the responders. Plasma AVP responses were completely abolished by hypophysectomy, although water intake by the dogs was normal. Histopathological examinations at 10 wk after hypophysectomy revealed that adrenocortical atrophy was much more pronounced in the corticotropic nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon. However, in all hypophysectomized dogs that were investigated, islets of pituitary cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH-immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anterior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the anterior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysiotropic stimulation are the most sensitive indicators for residual pituitary function after hypophysectomy, 4) small islets of pituitary cells in the sella turcica, containing corticotropic cells, are the most likely source of the attenuated corticotropic response that may occur after hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, despite the fact that the AVP response to hypertonic saline infusion is completely abolished.
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PMID:Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs. 906 51

Pituitary function was assessed before and after transsphenoidal hypophysectomy in 39 dogs with pituitary-dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hormones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH Pars intermedia function was assessed by measurements of basal plasma alpha-MSH concentrations and adrenocortical function by baseline urinary corticoid/creatinine ratios. At eight weeks after hypophysectomy basal plasma ACTH, cortisol, GH, LH, PRL, and TSH concentrations were significantly lower than before surgery. In seven dogs with elevated alpha-MSH concentrations, the values returned to the normal level after surgery. In the combined anterior pituitary function test there were no plasma GH, LH, PRL, and TSH responses to stimulation, whereas plasma ACTH and cortisol responses were small but significant. Remission of hyperadrenocorticism was obtained in 35 dogs and recurrences occurred in 3 of these within 16 months postoperatively. At 8 weeks after hypophysectomy, these 3 dogs were not discernible, with respect to residual pituitary and adrenocortical function, from the 32 dogs with persisting remission. Urinary corticoid/creatinine ratios in the latter group of dogs did not increase during 22 months after hypophysectomy. In contrast to the presurgical findings, at 8 weeks after hypophysectomy there were significant positive correlations between baseline urinary corticoid/creatinine ratios and basal levels and responses for ACTH, indicating return to normal function of the pituitary-adrenocortical axis. It is concluded that among the adenohypophyseal cells present in the sella turcica after hypophysectomy, the corticotropes have a distinct behavior. Much more so than the other cell types, the unaffected corticotropes tend to remain functional, or a repressed reserve fraction of corticotropes may become functional. This may be due to the removal of the hypothalamic influence of a postulated corticotropin-release inhibiting factor or a diminished inhibitory influence of a postulated paracrine factor. The corticotropes may maintain normocorticism, but may also lead to mild recurrence after relatively long periods of remission.
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PMID:Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. 948 98

Anterior pituitary hormone secretion is mainly regulated by hypothalamic releasing factors, which reach the pituitary via portal vessels. It has been demonstrated recently that these peptides can also be produced by the pituitary itself, thus possibly modulating hormone secretion in a paracrine/autocrine fashion. The object of this study was to seek evidence for the synthesis and secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary and to ascertain its biological relevance. Messenger RNA from adult rat anterior pituitary fragments and cell cultures was reverse transcribed and subjected to PCR amplification using primers specific to the rat CRH gene. As in the hypothalamus, a single 232-bp band was obtained. The correspondence of the amplified fragment to the sequence of the CRH gene was confirmed by Southern blotting and restriction enzyme digestion. Combined in situ reverse transcription-PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in corticotropes. Medium from anterior pituitary primary cultures contained approximately 7 pg/microg protein of CRH immunoreactivity which presented the same chromatographic profile on HPLC as the mature CRH peptide. Incubation of anterior pituitary cells with an antibody directed against CRH markedly reduced basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs. 1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10 vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/-0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to potassium and to forskolin was markedly blunted by the CRH antiserum as well as by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study demonstrates the presence of CRH mRNA in normal rat corticotropes and the secretion of the mature peptide by the anterior pituitary, pointing to the production of CRH at the site of its target cells. In addition, intrapituitary CRH contributes in a paracrine/autocrine fashion to ACTH secretion.
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PMID:Corticotropin-releasing hormone is produced by rat corticotropes and modulates ACTH secretion in a paracrine/autocrine fashion. 961 19

C-fos is an early expression oncogene that can be stimulated by a variety of regulators. It is expressed by subsets of all pituitary cells, with increased expression seen in proestrous rats. However, in freshly dispersed pituitary cells studied during different stages of the cycle, there is limited expression of fos by luteinizing hormone (LH) cells and little basal expression by cells with follicle-stimulating hormone (FSH) antigens. Proestrus is a time during which pituitary gonadotropes express peak levels of receptors for gonadotropin-releasing hormone (GnRH) and epidermal growth factor (EGF). We hypothesized that if GnRH or EGF stimulated fos activity in gonadotropes they would be most effective during the peak expression of their receptors. Anterior pituitaries were removed, cut into small pieces, and stimulated for 30 min. Total RNA was then collected and analyzed by Northern analysis. Both EGF and GnRH caused an increase in c-fos mRNA levels in the anterior pituitary gland compared with unstimulated pituitary glands assayed immediately after removal from the pituitary. However, the stimulatory effects were no greater than those seen with medium alone. This suggested that fos expression could be stimulated by local factors either in the pituitary or the medium itself. The second phase of the study focused on pituitary cells plated for 1 hr and then stimulated with EGF and GnRH for 15 min. Dual immunocytochemistry was done to learn which cell types expressed the fos proteins. After 15 min, EGF and GnRH both increased the percentages of fos-bearing cells above levels seen in medium alone. EGF stimulated fos proteins in subsets of FSH, adrenocorticotropin (ACTH), and growth hormone (GH) cells. GnRH increased fos proteins in subsets of ACTH and GH cells. These results suggest that EGF and GnRH may regulate fos expression, but not necessarily in gonadotropes. They also highlight the need for carefully timed experiments because endogenous factors in the pituitary itself may stimulate immediate early gene expression. (J Histochem Cytochem 46:935-943, 1998)
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PMID:Regulation of c-fos expression by EGF and GnRH in specific anterior pituitary cells from proestrous female rats. 967 43


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