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)

The relative contributions of the ovary and the adrenal gland to androgen overproduction in polycystic ovarian disease (PCOD) remain controversial. In this investigation, patients with proven PCOD were divided into two groups, (1) those with low dehydroepiandrosterone sulfate (DHEAS) levels and (2) those with high DHEAS levels, and compared with controls for their response to adrenocorticotropin hormone (ACTH) stimulation. Significant differences in weight, degree of menstrual disturbance, and basal progesterone levels distinguished the two groups with PCOD. Although no discrete enzyme block was unmasked by ACTH, marked differences in steroid production ratios were apparent between the low and high DHEAS PCOD groups. These results suggest that in PCOD with high DHEAS (1) substantial differences in adrenal steroidogenesis pathways occur, (2) increased progesterone as well as inappropriate estrogen feedback may contribute to chronic anovulation, and (3) serum DHEAS levels may be a helpful screen in discerning those patients who have a significant adrenal component to their hyperandrogenism and may benefit from adrenal suppression alone or in combination.
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PMID:Differential response to adrenocorticotropin hormone stimulation in polycystic ovarian disease with high and low dehydroepiandrosterone sulfate levels. 628 Oct 86

A group of 43 women of reproductive age with clinical signs of hyperandrogenism was treated with a low dose (7.5 mg daily) of prednisone. An acute dexamethasone (DEX) suppression-adrenocorticotropic hormone (ACTH) stimulation test was performed before and after a minimum of 2 months of prednisone administration. The therapy produced a significant decrease of plasma testosterone (T) levels in a majority of patients. During the treatment period DEX failed to induce further suppression, while ACTH caused a significant rise in plasma T levels. The cortisol (F) levels were suppressed during treatment, but their response to ACTH stimulation was similar to that observed prior to initiation of therapy.
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PMID:Response of the adrenal to adrenocorticotropic hormone (ACTH) in hyperandrogenic women treated chronically with low doses of prednisone. 628 71

Thirty-one cases of idiopathic hirsutism, characterized biochemically in the basal state by increased levels of urinary 3 alpha-androstane-5 alpha, 17 beta-diol and normal levels of the main androgens, were studied. In order to determine a possible etiologic heterogeneity of idiopathic hirsutism, pituitary gonadotropin responses to synthetic luteinizing-releasing hormone (LRH) and adrenal steroid responses to adrenocorticotropic hormone (ACTH) stimulation were evaluated and the results were compared to those in six normal women. On the basis of the results obtained in each hirsute patient after LRH and ACTH tests, two groups were identified. The majority, 23 of 31 hirsute patients (group I), had results similar to those in the control group. In the other eight patients (group II), biologic abnormalities were disclosed and suggested a partial adrenal 11 beta-hydroxylase defect in two patients, an incomplete form of adrenal 3 beta-ol deficiency in one patient, an adrenal hyperreactivity without evident cause in two patients, and polycystic ovary syndrome in association with an adrenal hyperreactivity in three patients. As a group, the eight patients showed ACTH-stimulated increments in testosterone, delta 4-androstenedione, dehydroepiandrosterone, and 17-ketosteroids that were significantly greater (p less than 0.01) than the mean responses in the control group. The conclusion is that some women who previously were designated as having "idiopathic" hirsutism had an adrenal and/or ovarian component to their hyperandrogenism which could be shown only by appropriate dynamic tests.
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PMID:Evidence for adrenal and/or ovarian dysfunction as a possible etiology of idiopathic hirsutism. 631 Oct 16

In 56 infertile women, aged 20 to 35, beta-endorphin (beta-EP) was determined out of the sample of peripheral blood plasma as well as the serum testosterone (T), progesterone (Prg), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG) at the medium (from the 6th to 9th day) and at the late follicular stage of the menstrual cycle (from the 10th to 14th day), the early luteal stage (from the 15th to 19th day) and at the late luteal stage of the cycle (from the 20th to 25th day). According to the gathered results of T, DHEA-S and the evaluated indexes of free androgenes of--FAI, women were grouped into two groups. Those with hyperandrogenism (n = 30) and those without hyperandrogenism (n = 26), with two subgroups: those with ovulation and those without it. Women with ovulation and without hyperandrogenism showed statistically significant higher concentration of beta-EP at the late luteal stage of the cycle in comparison with those without ovulation belonging to the same group (n = 9; 5.5 +/- 1.4 vs n = 7; 3.5 +/- 0.6; p < 0.01) as well as concerning the early luteal stage of their own cycle (5.5 +/- 1.4 vs 4.3 +/- 0.3; p < 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Levels of beta-endorphins in peripheral blood plasma in infertile women with and without symptoms of hyperandrogenism]. 773 49

Familial glucocorticoid resistance (FGR) is a rare hereditary disorder characterized by hypercortisolism and the absence of stigmata of Cushing's syndrome. The inability of glucocorticoids to exert their effects on target tissues is compensated for by increases in circulating corticotropin (ACTH) and cortisol, the former causing excess secretion of both adrenal androgens and adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is considerable variability in the clinical presentations of FGR ranging from asymptomatic, to isolated chronic fatigue and to hypertension with or without hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men it may lead to infertility and in children to precocious puberty. The reported molecular defects in FGR, such as point mutations and a microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance by, respectively, compromising the function of the GR or decreasing its intracellular concentration in glucocorticoid target tissues. Complete glucocorticoid resistance is believed to be incompatible with life in humans. Hence, the glucocorticoid resistance cases reported have been partial and of variable degree. The extreme variability in the clinical manifestations of the disorder can, additionally, be explained by differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps by different biochemical defects of the glucocorticoid receptor, causing selective resistance of certain glucocorticoid responses in specific tissues. Isolated tissue-resistance from a somatic mutation of the GR in a corticotropinoma from a patient with Nelson's syndrome was also found, suggesting that this may be a mechanism of tumorigenesis. There is additional evidence that defects of GR function can appear surreptitiously in a variety of clinical conditions, suggesting that glucocorticoid resistance in humans may be involved in the pathogenesis and/or clinical picture of a plethora of disease states, of which FGR is the archetype.
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PMID:Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms and implications for pathophysiology. 782 90

Adrenal hyperandrogenism is a common feature of patients with polycystic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivity to ACTH. Because enhanced ovarian androgen secretion does not appear to explain this phenomenon, we explored the role of estrogen in inducing enhanced adrenal sensitivity, in that a state of relative hyperestrogenism exists in PCO. Eight patients with PCO and seven matched controls received ovine corticotropin-releasing hormone (oCRH; 0.1 micrograms/kg) iv before and after hypoestrogenism was induced by leuprolide acetate (LA; 1 mg, sc, each day). In patients with PCO, a third oCRH test was repeated after transdermal estradiol (E2; 0.1 mg) had been applied for a week, during which time LA was continued. At baseline, patients with PCO had increased responses of 11 beta-hydroxyandrostenedione and dehydroepiandrosterone (P < 0.03 and P < 0.02) and increased delta maximal ratios of androstenedione (A4)/ACTH and dehydroepiandrosterone/ACTH (P < 0.01) after oCRH treatment. After LA administration to patients with PCO, these ratios were significantly suppressed (P < 0.01) and returned to baseline after E2 was added. There were no changes in controls. Steroid ratio responses to oCRH suggested that 17,20-desmolase activity (delta maximum change in the ratio of A4/17-hydroxyprogesterone) was lowered with estrogen suppression and increased again after transdermal E2 administration. There was a significant positive correlation between changes in E2 levels and delta maximum change in the ratios of A4/17-OHP after oCRH treatment, signifying 17,20-desmolase activity (r = 0.58, P < 0.02). In conclusion, these data provide evidence that estrogen is at least one factor that influences adrenal androgen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome.
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PMID:The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome. 785 27

The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testesterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effect also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 +/- 4.6 vs 12.4 +/- 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism. 816 60

Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease.
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PMID:Syndromes of glucocorticoid resistance. 818 39

Female adolescence is normally accompanied by increased adrenal and ovarian production of androgens. Indeed it is not uncommon in early to midpuberty to see typical features of adult polycystic ovary syndrome, with luteinizing hormone-driven ovarian hyperandrogenism, hyperinsulinemia, acne, anovulation, oligomenorrhea, and large, multifollicular ovaries. Unfortunately, no single prospective test can differentiate girls in whom this maturational stage is self-limited from those in whom it will progress to adult polycystic ovary syndrome with hirsutism and anovular infertility. An occasional hirsute adolescent will prove by corticotropin testing to have a nonclassical variant of adrenal 21-hydroxylase deficiency and will benefit from glucocorticoid therapy. The prevalence or even the existence of mild 11 beta-hydroxylase or 3 beta-hydroxysteroid dehydrogenase deficiency is more problematic. Given these difficulties of exact diagnosis and prognosis, therapy for the adolescent with mild hirsutism, acne, or oligomenorrhea should be conservative.
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PMID:Hyperandrogenism in female adolescents. 837 78

Hyperandrogenism, insulin resistance, and obesity are common features of polycystic ovarian syndrome (PCOS). This study was designed to investigate the relationship among these factors and how they might contribute to ovulatory dysfunction in PCOS. Adrenal androgen secretion and insulin resistance were quantified in oligomenorrheic women with PCOS and in three groups of eumenorrheic women: weight-matched hirsute women, obese nonhirsute women, and thin nonhirsute women. Adrenal androgen secretion was defined as the androstenedione response to synthetic corticotropin. Insulin resistance was estimated by calculating the area under the curve for serum insulin levels in response to a 75 g oral glucose load. The mean serum androstenedione response (nmol/L) to corticotropin in PCOS (5.6 +/- 1.3) was greater than that in eumenorrheic hirsute women (3.4 +/- 0.5; P < 0.10), obese nonhirsute women (1.8 +/- 0.8; P < 0.05), and lean nonhirsute women (1.9 +/- 0.5; P < 0.05). The serum androstenedione response was not correlated with body mass index (BMI). The area under the curve for serum insulin (mU/L.min/1000) in PCOS (29.1 +/- 5.3) was greater (P < 0.001) than in eumenorrheic hirsute women (9.1 +/- 1.7), obese nonhirsute women (5.8 +/- 1.0), and lean nonhirsute women (4.5 +/- 0.4). The serum insulin response was highly correlated with BMI (P < 0.001) in the three groups of obese women, but women with PCOS became significantly more insulin resistant with increasing BMI (P < 0.02). There was no correlation between adrenal androgen secretion and insulin resistance in any of the groups. We conclude that adrenal hyperandrogenism and insulin resistance are independent predictors of anovulation in hirsute women. These conditions are present in both oligomenorrheic and eumenorrheic hirsute women, but are present to a greater extent in anovulatory women. Obese women with PCOS also differ from eumenorrheic controls by developing a greater degree of insulin resistance as body mass increases.
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PMID:The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome. 838 5


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