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)

1. To evaluate different degrees of 21-hydroxylase (21-OH) deficiency we studied the 17-hydroxyprogesterone (17-OHP) and cortisol response to the adrenocorticotropin hormone (ACTH) stimulation test. In a study of 13 families we characterized the relatives of patients with classical 21-OH deficiency using HLA antigen typing and the ACTH test. The subjects were divided into five groups: 12 patients with the classical form, 11 patients with the nonclassical form, 38 heterozygotes, 6 normal homozygotes and 33 controls. 2. The 17-hydroxyprogesterone response to ACTH (mean +/- SD) varied as follows according to the degree of 21-OH deficiency: 25442 +/- 15718 ng/dl for the classical group, 4198 +/- 1637 ng/dl for the nonclassical group, 348 +/- 267 ng/dl for the heterozygotes, 127 +/- 81 ng/dl for normal homozygotes, and 164 +/- 120 ng/dl for the controls. Basal plasma cortisol did not differ among the five groups. The cortisol response to ACTH was not different among controls (30 +/- 8 micrograms/dl), normal homozygotes (28 +/- 7 micrograms/dl) and heterozygotes (26.5 +/- 7 micrograms/dl). The cortisol response was decreased in the patient groups and was lower in the classical (14 +/- 10 micrograms/dl) than in the nonclassical group (20 +/- 4 micrograms/dl). 3. In most families (11/13), HLA typing was informative in identifying the 21-OH deficiency containing haplotype, which correlated with the hormonal profile. In two families there was no correlation between the HLA genotype and the clinical expression of 21-OH activity for two HLA identical pairs of siblings.
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PMID:Adrenal response to adrenocorticotropin hormone and HLA typing of subjects with different degrees of 21-hydroxylase deficiency. 825 19

The nonsteroidal androgen-receptor antagonist nilutamide has previously been shown to inhibit adrenal androgen steroidogenesis in patients with prostatic carcinoma treated in combination with an LHRH agonist. In order to understand better the mechanisms subserving this observation, we have studied the effects of nilutamide alone on the serum concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), and DHEA-sulphate (DHEA-S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D-Trp-6-LHRH. In addition, the adrenocorticotropic hormone (ACTH)-stimulated adrenal response and the thyrotropin releasing hormone (TRH)-stimulated prolactin (PRL) response observed in the patients treated with nilutamide were compared with a control group of healthy age-matched controls. No significant variation in the basal concentrations of adrenal androgens occurred either within or between both treatment groups. In response to ACTH, a decreased 17-alpha hydroxyprogesterone (17-OHP) accumulation and an augmented A/17-OHP ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the partial removal of the 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PRL levels were not affected by the antiandrogen, but the response to TRH was increased. We conclude that no significant inhibition of adrenal androgen secretion occurs after nilutamide or LHRH agonist treatment. Rather, administration of the antiandrogen alone may partially remove the physiological decrease in adrenal androgen secretion observed in the elderly.
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PMID:Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion. 829 Mar 86

To determine whether abnormalities of hypothalamic-pituitary-adrenal axis function occur in type I diabetes mellitus, corticotropin, cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), and DHEA sulfate (DS) levels were measured after an intravenous (IV) injection of 1 microgram/kg human corticotropin-releasing hormone (CRH) in diabetic adolescents and normal age-matched subjects. CRH produced a consistent increase in corticotropin blood levels that was comparable in the two groups. In contrast, both baseline and stimulated cortisol concentrations were greater in diabetic patients. Levels of 17-OHP increased after CRH administration, and the magnitude of increase was similar in all subjects. Stimulation with CRH determined an attenuated integrated DS response in diabetics compared with normal subjects with a different pattern of the hormone secretion, whereas no differences in D4-A concentrations were detected between the two groups. DHEA serum levels of subjects from both groups underwent similar changes following administration of CRH. In conclusion, patients with type I diabetes have a discrete response of adrenal steroids to CRH stimulation that appears to be independent of corticotropin secretion. This phenomenon might be related to a direct effect of insulin on enzyme systems involved in the biosynthetic pathway of adrenal steroids or, alternatively, to an intra-adrenal CRH/corticotropin mechanism acting on the adrenal cortex in a paracrine manner.
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PMID:Adrenal steroid and adrenocorticotropin responses to human corticotropin-releasing hormone stimulation test in adolescents with type I diabetes mellitus. 841 66

The aim of this study was to classify the degree of 21 alpha-hydroxylase deficiency in patients suspected for non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women with polycystic ovary (PCO)-like symptoms and members of their families, of whom 12 were men), progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured at 0, 15, 30, 45 and 60 min after adrenocorticotropic hormone (ACTH) stimulation. The markers [(17-OHP at 30 min--17-OHP at 0 min) + (progesterone at 30 min--progesterone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to 17-OHP at 30 min (cortisol30/17-OHP30) were calculated and cluster analysis was performed using the above two markers and 17-OHP at 60 min (17-OHP60). Our patients were grouped by cluster analysis into four Groups: I, II, III and IV (n = 3, 11, 35 and 16, respectively) with (1) Gutai (mean +/- SE) 107.0 +/- 21.7, 29.9 +/- 4.4, 10.5 +/- 0.54 and 4.0 +/- 0.37 ng/dl per min, respectively, (2) 17-OHP60 169.7 +/- 28.3, 10.8 +/- 1.3, 4.6 +/- 0.2 and 3.7 +/- 0.4 ng/ml, respectively, and (3) cortisol/17-OHP30 0.97 +/- 0.28, 38.5 +/- 6.9, 82.3 +/- 5.5 and 112.0 +/- 8.9, respectively. All three markers showed highly significant differences between the four groups (p < 0.0001). The patterns of 17-OHP, cortisol and cortisol/17-OHP ratio following ACTH testing revealed the degree of 21-hydroxylase deficiency in every group. HLA typing effected in 20 studied individuals confirmed the classification derived from cluster analysis. Thus, it seems that Groups I, II and III include, respectively, patients with severe, mild and minimal forms of non-classic 21-hydroxylase-deficient CAH, while in patients of Group IV the hyperandrogenemic symptoms are of different etiology. In conclusion, the concurrent evaluation of the three markers together with the variations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH testing enhance the accurate identification of a patient suspected for non-classic 21-hydroxylase-deficient CAH in relation to the severity of the enzymatic defect.
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PMID:A contribution to the classification of cases of non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia. 854 Feb 93

Certain differences in regional fat distribution might be explicable by subtle hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. We examined prospectively PA function relative to abdominal obesity defined by waist-to-hip circumference ratio (WHR) in 71 normotensive men aged 30-55 years. Basal PA activity was assessed by measurements of serum cortisol and plasma corticotropin (ACTH) concentrations during the oral glucose tolerance test (OGTT). Functional activity was examined by dexamethasone suppression and ACTH stimulation tests; responses of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol, dehydroepiandrosterone (DHEA), and androstenedione were determined. When the subjects were divided into tertiles for the WHR, the ratio of mean ACTH to mean cortisol during the OGTT was increased (p < 0.05), and the ratio of urinary cortisol to body-mass index was decreased (p < 0.01), whilst the net increments of cortisol (p < 0.05) and 17-OHP (p < 0.05) from 0 to 60 min, as well as the ratio of 17-OHP to S increments (p < 0.05) after ACTH were elevated in the highest vs lowest WHR tertile. The ratio of mean ACTH to mean cortisol (r = 0.495; p < 0.001) during the OGTT, the ratio of net 17-OHP to S increments (r = 0.404; p < 0.001), and the net DHEA (r = 0.276; p = 0.020) and 17-OHP (r = 0.336; p = 0.005) responses to ACTH at 60 min correlated with WHR. In multivariate analyses the ratio of mean ACTH to cortisol, cortisol response to ACTH, and the ratio of net 17-OHP to S increments were all significant predictors of WHR independent of smoking, physical activity, and BMI explaining 49.0% of the variance in WHR. Thus, abdominal obesity may be associated with decreased activity of adrenal 21-hydroxylase. Either obesity-related functional alteration of 21-hydroxylase activity or the high carrier prevalence of genetic defects of this enzyme may explain these findings.
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PMID:Pituitary-adrenocortical function in abdominal obesity of males: evidence for decreased 21-hydroxylase activity. 880 94

The discovery of an asymptomatic adrenal mass (incidentaloma) during the investigation of an unrelated condition is relatively common. In this study, we report the clinical, radiologic, and endocrine evaluation of 38 patients (22 women and 16 men aged 24 to 84 years) with adrenal incidentaloma (size, 1 to 12 cm). The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, computed tomograpy (CT) scan and 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol(NP-59) and/or 131I-metaiodobenzylguanidine (MIBG) scintigraphy were performed. The endocrine evaluation indicated two cases of pheochromocytoma and four cases of preclinical Cushing's syndrome, three of which underwent surgery with histologic diagnosis of two adrenocortical adenomas and one carcinoma. Low levels of serum dehydroepiandrosterone sulfate (DHEA-S), associated with a markedly increased 17-hydroxyprogesterone (17-OHP) response to a corticotropin (ACTH) test, were found in patients with incidentaloma. On the basis of endocrine and morphologic data, 13 patients underwent surgical treatment: five adrenocortical adenomas (two functioning), two pheochromocytomas, two ganglioneuromas, one cortisol-secreting adrenal carcinoma, one lymphangiomatous cyst, one myelolipoma, and one hemorrhage were found. Careful diagnostic assessment of incidentally discovered adrenal masses must be performed to exclude the presence of malignant and/or functioning lesions and to verify the possibility that patients with incidentaloma have a genetic or acquired deficit of adrenal steroidogenic activity.
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PMID:Evaluation of hormonal function in a series of incidentally discovered adrenal masses. 900 78

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.
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PMID:Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women. 957 12

The purpose of this prospective study was to determine the incidence of any form of 21 alpha-hydroxylase deficiency among Greek women with hyperandrogenic symptoms, and to test the predictive value of basal serum 17-hydroxyprogesterone (17-OHP) in the early follicular phase as a screening index for patient preselection to adrenocorticotropic hormone (ACTH) testing. Eighty-eight unselected women with hyperandrogenic symptoms were examined in the Gynecological Endocrinology Unit of the Second Department of Obstetrics and Gynecology of Athens University. Using the ACTH-stimulated 17-OHP values at 60 minutes (17-OHP60) the study population was divided into four groups (A, B, C and D). Clinical and basal hormonal parameters as well as serum 17-OHP60 values and human leukocyte antigens were studied. Both clinical and basal hormonal parameters could be used to distinguish only patients with severe 21 alpha-hydroxylase deficiency (group A). In contrast, patients with moderate non-classical congenital adrenal hyperplasia (NC-CAH; group B), heterozygotes for NC-CAH (group C), and unaffected females (group D) can be diagnosed and classified only by serum 17-OHP60 values. In conclusion, the incidence of NC-CAH in Greek females with hyperandrogenic symptoms is 3.4%. The positive predictive value of basal 17-OHP is only 13% for this disease. Only 17-OHP60 helps to diagnose and classify moderate and mild forms of NC-CAH. Thus, it seems that ACTH testing is imperative in every subject suspected of this enzymatic disorder.
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PMID:The incidence of 21 alpha-hydroxylase deficiency in Greek hyperandrogenic women: screening and diagnosis. 961 Apr 21

It is well known that normal and mildly elevated luteinizing hormone (LH) levels induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha-hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has been shown in both in vitro and in vivo studies in animals and in in vitro studies in women that high LH concentrations have opposite effects on these enzymes. These LH down-regulating effects appear to be more marked on 17,20-lyase than on 17-hydroxylase. Finally, these LH effects have not been reported in vivo in women. Therefore, we investigated the relationships between serum LH levels and serum 17-OHP and androstenedione concentrations in 263 consecutive hirsute women (HW) with normal serum 17-OHP responses to acute adrenocorticotropin (ACTH) stimulation. The patterns of basal serum steroid concentrations differed according to the basal serum LH levels. Indeed, for relationships between LH and 17-OHP concentrations, a positive correlation (P < 0.001) was found between the levels of these parameters when LH levels ranged from 0.2 to 9.0 IU/l. Conversely, for LH levels greater than 9.0 to 21.0 IU/l, LH values were negatively correlated (P<0.001) with 17-OHP concentrations. Similar results were observed for relationships between LH and androstenedione levels but the LH peak level related to decreasing androstenedione concentrations was 12.0 IU/l. Finally, the mean 17-OHP level in patients with LH levels which induced marked P450 down-regulation (i.e. more than 12 IU/l) was similar to that in patients with LH levels within the normal range (i.e. less than 6 IU/l). In contrast, the mean androstenedione level in the former patients was markedly higher (P<0.001) than that in the latter patients. In conclusion, as previously reported in in vitro studies, this in vivo study indicates that LH induces stimulating and down-regulating effects on both ovarian delta(4)17-hydroxylase and delta(4)17,20-lyase activities as serum LH levels gradually increase. However, in contrast to in vitro studies, LH levels which induce P450 down-regulation appear to be less effective on delta(4)17,20-lyase than on delta(4)17-hydroxylase in HW. This strongly suggests that serum factors induce, in most HW, a marked increase in delta(4)17,20-lyase, but not in delta(4)17-hydroxylase, activity leading to both partial impairment of LH-induced delta(4)17,20-lyase down-regulation and complete LH-induced delta(4)17-hydroxylase down-regulation in these patients.
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PMID:High serum luteinizing hormone levels induce ovarian delta4 cytochrome P450c17alpha down-regulation in hirsute women: complete effect on 17-hydroxylase and partial effect on 17,20-lyase. 975 40

Adrenal function may be abnormal in women with polycystic ovary syndrome (PCOS). This study aims to evaluate adrenal steroid response to the adrenocorticotropic hormone (ACTH) stimulation test and to find out the effect of high serum testosterone levels on adrenal response. We have also investigated any subtle enzyme deficiency by extending blood sampling to 2 h with 30 min intervals following ACTH administration. Twenty-eight women with PCOS and 18 healthy controls without hirsutism and oligomenorrhea were included in the study. After determining their serum basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and progesterone, ACTH stimulation test was performed. The change in serum 17-OHP and the summed rate of change in serum 17-OHP and progesterone levels were estimated and 95th percentile for each value was computed. Women with PCOS were heavier and more hirsute than controls (p < 0.01, p < 0.001, respectively). Serum basal LH, LH:FSH ratio, testosterone (p < 0.001, for all), DHEAS (p < 0.01), and 17-OHP (p < 0.05) were higher in women with PCOS. All of the 17-OHP measurements, including basal and each 30 min interval after the administration of ACTH, were higher in women with PCOS than those of healthy controls (p < 0.05, p < 0.002, p < 0.001, p < 0.015, p < 0.018, respectively). However, the incremental changes in serum 17-OHP30-0, 17-OHP60-0, 17-OHP90-0, 17-OHP120-0, and the summed rate of change in serum 17-OHP and progesterone in women with PCOS were not different from those in healthy controls. The incremental response in terms of serum progesterone, DHEAS, and testosterone levels to the ACTH stimulation test for each 30 min interval was not different in women with PCOS than in healthy controls. We were not able to show any critical value for serum basal testosterone and DHEAS levels that would effect response to ACTH stimulation in terms of 17-OHP levels. We have concluded that extending the duration of blood sampling up to 2 h has no advantage in evaluating adrenal steroid response to ACTH stimulation. Since serum 17-OHP levels remain within normal limits in response to ACTH stimulation, the origin of elevated serum basal 17-OHP levels may be polycystic ovaries. Elevated serum testosterone level does not have any adverse effect on adrenal function. Serum progesterone measurement seems to have no place in the diagnosis of 21-hydroxylase deficiency. Adrenal androgenic response to ACTH stimulation is normal in women with PCOS.
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PMID:Adrenal androgenic response to 2-hour ACTH stimulation test in women with PCOS. 979 31


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