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)

We investigated the effects of various hormones and growth factors on aromatase activity in cultured human skin fibroblasts. Several potential trophic factors were tested for their ability to modify basal aromatase activity or the response to dibutyryladenosine 3',5'-cyclic monophosphate and dexamethasone because (i) no endogenous ligand has been identified that is responsible for stimulating aromatase activity in the periphery, and (ii) dexamethasone and cAMP analogs can increase this enzyme's activity in fibroblasts. The effect of insulin and insulin-like growth factors were examined in closer detail because of the clinical association between insulin and hyperandrogenism. Pituitary hormones and hypothalamic releasing factors, such as human ACTH (10 nM), beta-endorphin (10 nM), beta-lipotropin (10 nM), alpha-MSH (10 nM), gamma 3-MSH (10 nM), ovine luteinizing hormone (10 ng/ml), ovine follicle-stimulating hormone (10 ng/ml), ovine thyroid-stimulating hormone (10 ng/ml), rat growth hormone (10 ng/ml), rat prolactin (10 ng/ml), rat corticotropin-releasing factor (10 nM), luteinizing hormone-releasing factor (10 nM), thyrotropin-releasing factor (10 nM), human growth hormone-releasing factor (10 nM), and somatostatin (10 nM), have no significant effects on aromatase activity. Porcine inhibin A (10 ng/ml) and porcine activin AB (10 ng/ml), two ovarian hormones with structural transforming homology to transforming growth factor-beta, also have no effect on aromatase activity. Although basic fibroblast growth factor (1-100 ng/ml), acidic fibroblast growth factor (1 ng/ml), epidermal growth factor (1 ng/ml), platelet-derived growth factor (1 ng/ml), tumor necrosis factor (1 ng/ml), and transforming growth factor-beta 1 (1 ng/ml) have no effect on basal aromatase activity in human skin fibroblasts, all of these growth factors inhibited the ability of dibutyryladenosine 3',5'-cyclic monophosphate to stimulate aromatase activity. In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM). Thus, there is a clear distinction between the effects of dexamethasone and cAMP on peripheral aromatase. On the basis of the results presented here, it is interesting to speculate that the hyperandrogenism that is often associated with insulin resistance may be due to a combination of growth factor-mediated inhibition of aromatase activity and the failure of peripheral tissues to respond to insulin and metabolize androgens to estrogens.
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PMID:Growth factor-mediated regulation of aromatase activity in human skin fibroblasts. 167 98

To determine whether the adrenal androgen 11 beta-hydroxyandrostenedione is a more sensitive and specific marker than dehydroepiandrosterone sulfate, we compared these serum androgens in 81 women with anovulatory hyperandrogenism before treatment, after corticotropin and corticotropin-releasing-factor stimulation, and after short- and long-term dexamethasone suppression. Of all subjects, 65% and 57% had elevated levels of 11 beta-hydroxyandrostenedione (greater than 2.0 ng/ml) and dehydroepiandrosterone sulfate (greater than 2.8 micrograms/ml), respectively. However, 11 beta-hydroxyandrostenedione and dehydroepiandrosterone sulfate levels did not correlate in either the women with hyperandrogenism (r = 0.12) or the 26 normal women (r = 0.29). After 0.25 mg corticotropin was administered intravenously (n = 16), 11 beta-hydroxyandrostenedione increased by 157% +/- 53% (mean +/- SEM), whereas dehydroepiandrosterone sulfate, androstenedione, dehydroepiandrosterone, and cortisol increased by 6% +/- 2%, 46% +/- 10%, 416% +/- 80%, and 2326% +/- 371%, respectively. After intravenous administration of 100 micrograms corticotropin-releasing factor to eight patients, the percent change from baseline level to peak was 148% +/- 26%, 24% +/- 5%, 61% +/- 15%, 117% +/- 15%, and 116% +/- 18% for 11 beta-hydroxyandrostenedione, dehydroepiandrosterone sulfate, androstenedione, dehydroepiandrosterone, and cortisol, respectively. After 2 mg dexamethasone for 3 days (n = 10), 11 beta-hydroxyandrostenedione, dehydroepiandrosterone sulfate, androstenedione, and testosterone were suppressed by 95% +/- 2%, 74% +/- 3%, 51% +/- 9%, and 32% +/- 9%, respectively. Suppression with 0.5 mg dexamethasone for 3 months lowered 11 beta-hydroxyandrostenedione and dehydroepiandrosterone sulfate levels equally by 50% +/- 14% and 62% +/- 12%, respectively. 11 beta-Hydroxyandrostenedione is a useful marker of adrenal androgen secretion with a calculated sensitivity and specificity greater than that of dehydroepiandrosterone sulfate. The greater sensitivity of 11 beta-hydroxyandrostenedione over dehydroepiandrosterone sulfate to adrenal stimulation and suppression suggests its unique diagnostic use.
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PMID:Is 11 beta-hydroxyandrostenedione a better marker of adrenal androgen excess than dehydroepiandrosterone sulfate? 183 6

Normal values in endocrine testing are the most important precondition for the recognition of disorders of the endocrine system. To establish a reference range for adrenocorticotropic hormone (ACTH) stimulation tests, an intravenous and intramuscular ACTH stimulation test was conducted in 29 female volunteers without hyperandrogenism. A total of 25 IU of ACTH were administered intravenously or intramuscularly and blood sampling was performed before, 1 h and 2 h after ACTH injection. The test was performed on days 3-5 of the menstrual cycle. The following steroid hormones were assessed in the serum: 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, testosterone, free testosterone and 5 alpha-dihydrotestosterone. The normal range was defined by the interval between the 5th and 95th percentiles; additionally the 1st, 25th, 50th, 75th and 99th percentiles are reported. A significant increase of serum hormone levels after ACTH administration could be observed for the following hormones: cortisol, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and dehydroepiandrosterone. There was no rise after ACTH application for testosterone, 5 alpha-dihydrotestosterone and free testosterone. It could be shown for all hormones that there was no significant difference between the serum levels that were reached after intravenous and intramuscular ACTH injection. Neither could we find a significant difference in the relative increase of the serum hormones when stimulation values were related to basal values. Since in most studies with ACTH stimulation tests, only the serum values 1 h after ACTH application are measured, we investigated whether the measurement of steroid hormones 2 h after ACTH application gave further information. We could demonstrate that for most measured serum hormones the majority of the volunteers had the maximal response 2 h after ACTH application, no matter whether ACTH was injected intramuscularly or intravenously. As a conclusion, we recommend the measurement of the respective hormones not only 1 h but also 2 h after ACTH stimulation. Since there is no increase after ACTH stimulation for total testosterone, free testosterone and 5 alpha-dihydrotestosterone, it is sufficient to assess the basal values of these hormones. Excessive adrenal response is reflected by dehydroepiandrosterone, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and cortisol.
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PMID:Normal values for a short-time ACTH intravenous and intramuscular stimulation test in women in the reproductive age. 196 39

Stress has been implicated in the physiopathology of the ovarian androgenic syndrome. To explore further this notion, we compared the behavioral and endocrine responses to a mental stressor between women with hyperandrogenism (n = 13) and normals (n = 11). The standardized psychological stimulus produced higher levels of anxiety in the hyperandrogenic group than in controls. The endocrine (cortisol, prolactin, growth hormone, beta-endorphin) responses poststressor were definitely dissociated. Both groups showed a comparable anticipatory stress cortisol-secretion response. The cortisol release was greater following the mental stressor in the hyperandrogenic group than in the normals. Thus, hyperandrogenic women appear to have an abnormally affected pituitary-adrenal activation, which may play a role in the pituitary-ovarian disruption characteristic of the ovarian androgenic syndrome.
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PMID:Endocrine and behavioral responses to psychological stress in hyperandrogenic women. 213 94

Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17 alpha) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17 alpha.
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PMID:Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. 218 40

The basal levels of beta-endorphin were measured in 43 women with various grades of hirsutism. The degree of the hair growth, weight, body mass index (BMI), age, menstrual regularity and various androgen or pituitary hormone values were not sufficient to distinguish the patients with regard to their beta-endorphin levels. In 11 patients a clinical diagnosis of a polycystic ovarian disease-like disorder was made. The beta-endorphin values of these women did not differ from those of 10 women with adrenal hyperandrogenism or the other hirsute women with identical BMI. Plasma beta-endorphin was significantly higher in obese hirsute patients with a low testosterone/sex-hormone-binding globulin (T/SHBG) ratio than in lean, nonhirsute women with a higher T/SHBG ratio (P less than 0.02). The findings suggest a possible but complex connection of beta-endorphin with some forms of female hyperandrogenism.
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PMID:Beta-endorphin basal levels in hirsute women. 293 33

We previously reported that circulating beta-endorphin levels are increased in obese hirsute women and that plasma immunoreactive insulin (IRI) levels are increased in proportion to the degree of hyperandrogenism in women with the polycystic ovary (PCO) syndrome. We, therefore, tested the hypothesis that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in this syndrome. In the first study, acute naloxone administration significantly reduced the plasma IRI response and IRI/glucose ratio in three euglycemic obese women with PCO and acanthosis nigricans (AN) and marked insulin resistance, but did not alter the glucose response. Naloxone had no effect on these parameters in the normal weight control subjects. In the second study, nalmefene, a new, orally active opiate antagonist, reduced IRI and the IRI/glucose ratio in four women with PCO-AN and marked hyperinsulinemia in a randomized, double blind, crossover protocol. We conclude that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in PCO-AN.
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PMID:Reduction of hyperinsulinemia and insulin resistance by opiate receptor blockade in the polycystic ovary syndrome with acanthosis nigricans. 353 80

Total 24-hour urinary 17-ketosteroid (17-KS) and serum testosterone (T), androstenedione (A), and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured before and after the administration of Cortrosyn and dexamethasone in 46 hirsute and 18 nonhirsute women. Both the baseline urinary 17-KSs and serum androgen levels were significantly higher (P less than 0.05) in hirsute than in nonhirsute subjects. In 58% of the patients in the hirsute group serum androgen concentrations were found to be elevated, while 17-KS levels in 24-hour urine collections were within normal limits. In 87% of our hirsute subjects at least one serum androgen was elevated. Serum DHEA-S concentration was elevated in almost half of the patients with hirsutism. For the evaluation of hyperandrogenism, measurements of serum androgens give more accurate information to the clinician. Dynamic stimulation-suppression studies do not appear to offer any better understanding of the type of androgens involved or a rational guide to the choice of therapy. Hirsute patients were found to be responding less to corticotropin stimulation in comparison to nonhirsute patients. The stimulation rate was significantly higher in 17-KS, A, T, and DHEA-S concentrations in nonhirsute than in hirsute patients.
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PMID:Hirsutism: diagnostic approach and stimulation-suppression dynamics of androgens in the female. 612 19

The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17-hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11-deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17-delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism.
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PMID:Abnormal adrenal responses to adrenocorticotropic hormone in hyperandrogenic women. 624 65

A group of 106 consecutively seen hyperandrogenic women were subjected to an acute adrenal suppression and stimulation test. The results of these tests were analyzed with respect to androgen suppression achieved after chronic glucocorticoid therapy in the same patients. The data suggested that an acute dexamethasone test may identify the group of hyperandrogenic women who respond poorly to chronic glucocorticoid therapy. This group of patients were found to have elevated luteinizing hormone (LH) levels and LH/follicle-stimulating hormone (FSH) ratios, suggesting the possibility of an LH-related hyperandrogenism. In patients whose elevated testosterone levels were suppressed by dexamethasone, adrenocorticotropic hormone (ACTH) induced a prompt return of the testosterone levels to baseline, suggesting an ACTH-dependent hyperandrogenism. In these patients, the degree of testosterone suppression after dexamethasone was not quantitatively related to the degree of testosterone suppression after chronic glucocorticoid therapy. In all cases chronic therapy resulted in a greater suppression of androgen levels than the acute dexamethasone test. In conclusion, an acute dexamethasone suppression test appears to be of clinical value in the management of the hyperandrogenic female, particularly in identification of women who will not respond to chronic glucocorticoid suppression therapy.
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PMID:The prognostic value of acute adrenal suppression and stimulation tests in hyperandrogenic women. 627 99


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