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)

Cortisol concentrations in human seminal plasma, as estimated by the very specific Amersham 'Amerlite' luminescence immunoassay, were 176 +/- 43 (85-260) nmol/l, that is, 63.7 +/- 15.5 (31-94) ng/ml (mean +/- SD, n = 21). This is about 60% of random levels in blood serum and is the first description of cortisol in seminal fluid. In human amniotic fluid at 16-22 weeks of gestation, cortisol concentrations were lower, at 72.6 +/- 14.6 (63-124) nmol/l, that is, 29.3 +/- 5.3 (23-45) ng/ml (n = 21). Concentrations were about 15% of random maternal serum levels in the second trimester of pregnancy. The cortisol concentrations in both fluids were considerably higher than those reported for saliva, which has a mean of about 10 nmol/l. Transcortin (corticosteroid binding globulin, CBG), has been found in human seminal plasma and amniotic fluid for the first time. Concentrations were low, with values up to 12 micrograms/ml, with no significant difference between the two fluids, when using the IRE-Megenix monoclonal iodinated radioimmunoassay. Transcortin concentrations were about 10% of levels in non-pregnant blood serum, compared with about 0.1% for saliva. The higher concentrations of transcortin could perhaps account for the greater diffusion of cortisol into seminal plasma and amniotic fluid. The presence of beta-endorphin, ACTH and cortisol in amniotic fluid, seminal fluid, ovarian follicular fluid, endometrial fluid and gastric fluid may possibly, indicate the existence of a small paracrine ACTH-cortisol axis in the relevant secretory tissues.
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PMID:Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays. 224 Jun 17

To assess the effects of age on both the pituitary ACTH response to corticotropin-releasing hormone (CRH) and the secretory responses of cortisol (F) and dehydroepiandrosterone (DHEA) to endogenous rises in ACTH, we measured evening basal and ovine CRH (oCRH; 1 mu/kg)-stimulated plasma concentrations of ACTH,F, and DHEA in 49 healthy men, aged 21-86 yr. By analysis of variance, we found no change with age in either the basal concentration of ACTH or the magnitude of the peak ACTH response to oCRH. Older men had higher basal F levels (P less than 0.05), while basal plasma levels of CBG and ratios of F to CBG did not vary significantly with age (P greater than 0.1). We also found no significant increase with age in the magnitude of the peak F response to oCRH (P greater than 0.2), although peak F responses occurred significantly earlier (P less than 0.03) in the older men. Basal plasma levels of DHEA decreased significantly with age (P less than 0.001), as did the magnitude of peak DHEA responses to endogenous ACTH rises (P less than 0.01). There was no alteration in the timing of the peak DHEA response with age (P greater than 0.7). We conclude that while ACTH and F responses to evening injections of oCRH are well maintained in healthy aging men, that of DHEA is discordantly decreased. The present findings are compatible with the hypotheses that there is a diminished sensitivity of ACTH secretion to negative feedback regulation by glucocorticoids in older men, and there is an ACTH-independent age-related diminution in adrenal androgen secretion.
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PMID:Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin-releasing hormone in healthy aging men. 300 57

The possible role of steroid binding proteins in the hormonal secretion process of a steroidogenic tissue was examined using bovine adrenocortical cell suspensions, either under basal conditions or in the presence of half-maximally active concentration (1 x 10(-9) M) of synthetic adrenocorticotropic hormone (ACTH). Three types of plasma cortisol binding proteins were used, namely bovine serum albumine (BSA), purified transcortin (CBG) and purified anticortisol immunoglobulins (IgG). When added to the incubation medium, CBG (at 1 x 10(-10) to 2 x 10(-9) M cortisol binding sites) and anticortisol IgG (at 4.8 x 10(-10) to 3 x 10(-9) M cortisol binding sites) did not influence either the basal nor the ACTH-stimulated net cortisol production of the cell preparations. Whereas crystallized and delipidated BSA showed also no effect, crude commercial BSA preparation (Cohn fraction V) exhibited an ACTH-like cofactor effect which resulted in a marked increase in the net cortisol production by stimulated cells. These observations might be explained by the presence in crude BSA of lipoprotein-cholesterol complexes, possibly acting as an extracellular source of cholesterol available for corticosteroidogenesis. It may be concluded that specific high affinity cortisol binding systems present outside adrenocortical steroidogenic cells do not influence their secretory activity under short term in vitro condition. In addition, it can be stressed that use of ill defined protein preparations (e.g. crude BSA) may lead to artifactual observations in the study of the differentiated functions of isolated steroidogenic cells.
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PMID:Effect of corticosteroid binding proteins on the steroidogenic activity of bovine adrenocortical cell suspensions. 628 6

The plasma concentration of N-terminal beta-lipotrophin (beta-LPH), total and protein unbound cortisol, progesterone and the transcortin (CBG) binding parameters have been measured in 21 women in the early follicular phase and in 70 pregnant women at various stages of pregnancy. Results showed that the plasma CBG binding capacity and the concentrations of total cortisol and progesterone increased significantly at each trimester of pregnancy while the plasma concentration of unbound cortisol increased significantly only in the 2nd and the 3rd trimesters of pregnancy. In addition, a significant increase of N-terminal beta-LPH level was observed during the 3rd trimester. By chromatography, it is demonstrated that during the 3rd trimester of pregnancy the beta-LPH/gamma-LPH molar ratio decreases dramatically and that the increase of N-terminal beta-LPH concentration is mainly due to a two fold increase in gamma-LPH concentration.
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PMID:Increased plasma concentration of N-terminal beta-lipotrophin and unbound cortisol during pregnancy. 671 91

In domestic ruminants such as the sheep, birth is effected through sequential maturation of the foetal hypothalamic-pituitary-adrenal (HPA) axis, leading to the increased output of cortisol. Factors regulating foetal pituitary adrenocorticotrophin (ACTH) secretion have been delineated, and these include corticotrophin releasing hormone (CRH), arginine vasopressin, prostaglandin (PG) E2 and endogenous opioids. The pre-partum increase in foetal plasma ACTH is associated with a rise in pro-opiomelanocortin (POMC) mRNA in the foetal pars distalis, and with an altered pattern of POMC post-translational processing. Foetal adrenal activation results from an increase in ACTH receptors and enhanced coupling through the Gs protein to adenylate cyclase, and increased expression of key steroidogenic enzymes including P450c17. Cortisol modulates the mechanism by which ACTH activates foetal adrenal function, through specific glucocorticoid receptors (GR) in the foetal adrenal cortex. Although the numbers of GR change with gestation, the relative abundance of GR mRNA does not, pointing to post-translational regulatory mechanisms. Cortisol also stimulates an increase in the concentration of its own high affinity binding protein (corticosteroid binding globulin; CBG) in the foetal circulation, apparently by increasing CBG gene expression in the foetal liver, and by altering the extent of foetal CBG glycosylation in a manner that would be expected to decrease the metabolic clearance of this glycoprotein. Clear evidence for placental CRH and ACTH production is lacking in sheep, but PGE2, produced in increasing amounts by the placenta during late pregnancy, may augment the drive to HPA maturation. Aspects of the maturational pathway of cortisol biosynthesis have been described in other species, including the horse, and some comparison is made with the more detailed information currently available from species such as the sheep.
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PMID:Foetal endocrine maturation. 907 35

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.
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PMID:Glucocorticoid receptors, fibromyalgia and low back pain. 948 5

Hippocampal mineralocorticoid (MRs) and glucocorticoid receptors (GRs) have been demonstrated to regulate the activity of the hypothalamus-pituitary-adrenocortical (HPA) system. To elucidate the role of the hippocampal MR in the circadian activity of the human HPA system, we studied diurnal secretory profiles of corticotropin (ACTH) and cortisol in 10 healthy male humans before and after an 8-day treatment with the MR antagonist spironolactone. 24-hour blood sampling at 30-min intervals was performed for estimation of cortisol (q30) and ACTH (q120). Saliva cortisol was measured for estimation of unbound cortisol. At the end of the 24-hour sampling period a corticotropin-releasing hormone (CRH) challenge was performed. High plasma concentrations of the active metabolite canrenone were achieved (begin of sampling: 2,653 +/- 693 nmol/l; end of sampling: 747 +/- 177 nmol/l). There was a significant increase in the diurnal minima (37.1 +/- 13.3 vs. 23.7 +/- 8.9 nmol/l, p < 0.02) and mean cortisol (193.5 +/- 25.8 vs. 173.0 +/- 23. 0 nmol/l, p < 0.03) plasma concentrations. However, the diurnal peak concentrations and pulsatile secretory features were unchanged after spironolactone treatment. For saliva cortisol, the only significant treatment difference was a decrease in the diurnal amplitude of cortisol relative to the diurnal mean concentration (2.56 +/- 0.47 vs. 3.11 +/- 0.87, p < 0.03). After spironolactone treatment there was a decrease in diurnal mean ACTH concentrations (46.2 +/- 14.4 vs. 41.8 +/- 10.3 pmol/l). There was no difference in the ACTH and cortisol response after infusion of CRH before and after spironolactone treatment. CBG plasma concentrations were significantly increased (22.4 +/- 2.3 vs. 19.2 +/- 2.7 mg/l, p < 0. 01) after spironolactone treatment, which possibly contributed to the observed increase in plasma cortisol. In summary, as predicted from animal studies we found significant effects of MR antagonization to be restricted to time windows of low HPA system activity. These findings are similar to the effects of aging upon the HPA system. However, the effect of spironolactone treatment was small, suggesting that the HPA system activity in humans is modulated but not regulated by the hippocampal MR.
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PMID:Mineralocorticoid receptor also modulates basal activity of hypothalamus-pituitary-adrenocortical system in humans. 982 3

The objectives of this study were to develop an assay for the direct measure of porcine corticosteroid-binding globulin (pCBG) and to confirm age-related changes in plasma pCBG concentration. Isolation and purification of pCBG from plasma was performed by affinity chromatography and HPLC-DEAE anion exchange techniques. Analysis by SDS-PAGE revealed two polypeptides (54 and 59 kDa) having similar amino acid homology (>50%) to previously reported sequences of seven mammalian species for the first 33 amino acids. Porcine CBG (20 ng/well) was immobilized to microtiter plates and standards or samples added along with rabbit antiserum developed against the purified pCBG. Goat anti-rabbit IgG-alkaline phosphatase conjugate was added followed by p-NPP substrate. The resultant color development was read at 405 nm. Intra- and interassay coefficients of variation (n=26) of a pooled sample were 10 and 15%, respectively. Age-related changes (P<0.001) in plasma pCBG concentration (n=203) from day 3 through 168 of age confirmed that, in the pig, changes seen in the percent distribution of cortisol among protein bound and free forms around day 28 of age are associated with an increase in CBG concentration.
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PMID:Age-related changes in porcine corticosteroid-binding globulin (pCBG) as determined by an enzyme-linked immunosorbent assay. 1274 50

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (p<0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (p<0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (p<0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p<0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.
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PMID:Testosterone suppression of CRH-stimulated cortisol in men. 1584 Nov 3

Corticosteroid-binding globulin CBG is expressed in magnocellular hypothalamic nuclei, in part colocalized with vasopressin (VP) and oxytocin (OT). Here we subjected intact adult male rats to chronic osmotic stress to determine effects on distribution of CBG in VP and OT neurons and in neurons expressing corticotropin- releasing hormone (CRH). Drinking 2% NaCl solution for seven days resulted in increased CBG-immunoreactivity in magnocellular neurons. Triple immunofluorescence revealed increased colocalization with either VP, OT or CRH. Colocalization of CRH with VP was found only in a small portion of parvocellular neurons in the PVN. Most of the CBG-immunostained neurons within the magnocellular nuclei were devoid of CRH-immunoreactivity. Increased numbers of axons with colocalization of CBG and VP or OT were found in the internal zone of the median eminence (ME) of osmotically challenged rats. The external zone of the ME showed numerous CRH-positive neuronal projections. A small portion of them contained also CBG-immunofluorescence in both experimental animals and controls. Immunoassays of cerebrospinal fluid showed increased levels of CBG in osmotically stressed animals. Our observations suggest that hypothalamic CBG expression is malleable to functional status and that coexpression with the magnocellular peptide hormones may be of significance for endocrine stress response.
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PMID:Osmotic stress induces corticosteroid-binding globulin expression in the rat hypothalamo-hypophyseal system. 3058 17


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