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)

Ketoconazole is an antifungal agent that, in high doses, inhibits testicular and adrenal steroid synthesis. The ability of ketoconazole to block steroid synthesis has prompted us to use it in the treatment of advanced prostatic carcinoma. This study was designed to determine the site of steroid synthetic blockade that was induced by ketoconazole. Twelve patients with metastatic prostate carcinoma on long term high dose ketoconazole therapy were compared with 12 control volunteers. Values of serum progesterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulphate, testosterone, and cortisol were measured in a baseline state and after Cosyntropin and human chorionic gonadotropin stimulation. Baseline data showed that serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulphate were lower and that plasma progesterone, luteinizing hormone, and adrenocorticotropin were higher in the ketoconazole group. With Cosyntropin, plasma cortisol, androstenedione, and dehydroepiandrosterone sulphate increased only in the control group. With human chorionic gonadotropin, testosterone increased only in the control group. Basal 17-hydroxyprogesterone and progesterone rose after Cosyntropin only in the ketoconazole group. Following human chorionic gonadotropin, progesterone rose in the ketoconazole group but not in the control group. These results suggest that ketoconazole is a potent inhibitor of steroid synthesis. The major site of action appears to be in the inhibition of 17-20 desmolase. A moderate blockade of 17-hydroxylase may be present. There is a marked inhibition of 21- and/or 11-hydroxylase. The ability of ketoconazole to inhibit steroid synthesis should have therapeutic potential in the treatment of steroid dependent disease. Frequent high dose ketoconazole therapy can inhibit adrenal steroid synthesis, which can be important for patients undergoing stressful situations.
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PMID:Steroid synthesis inhibition by ketoconazole: sites of action. 296 91

Controversy surrounds the issue of whether beta-endorphin affects adrenal steroidogenesis. Recent work has both supported and refuted the claim that beta-endorphin stimulates a rise in serum aldosterone. We investigated the role of beta-endorphin in adrenal steroidogenesis by examining its potential modulation of the response of serum cortisol to exogenous ACTH (Cosyntropin). Four of five normal men received: 1) synthetic beta-endorphin (1 microgram/kg X min) for 30 min, followed by a bolus dose of 0.2 micrograms ACTH; 2) beta-endorphin (100 micrograms, iv), followed by 0.2 micrograms ACTH iv; 3) 0.2 micrograms ACTH iv; and 4) beta-endorphin (100 micrograms iv) alone. The integrated cortisol response to exogenous ACTH, calculated as the area under the cortisol response curve, was significantly less when the ACTH infusion was preceded by the 30-min beta-endorphin infusion than when administered alone [163 +/- 50 (SE) microgram/dl X min vs. 282 +/- 51 micrograms/dl X min, respectively; P less than 0.01]. By contrast, there was no difference between the integrated cortisol response to exogenous ACTH alone and exogenous ACTH after the bolus dose of beta-endorphin (282 +/- 51 vs. 293 +/- 39 micrograms/dl X min, respectively). Beta-Endorphin (30-min infusion or 100-micrograms bolus dose alone) caused no change in serum aldosterone, dehydroepiandrosterone, or PRA. Serum PRL levels, however, were raised significantly (P less than 0.05) by the 30-min infusion of beta-endorphin. The infusion and bolus doses of beta-endorphin raised plasma beta-endorphin levels to over 100,000 pg/ml and 5,000 pg/ml, respectively. We conclude that very high plasma levels of beta-endorphin may influence the response of cortisol to ACTH through a direct effect on the adrenal cortex. However, even in disease states such as Addison's and Nelson's diseases, such levels of plasma beta-endorphin are not known to be achieved.
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PMID:Beta-endorphin attenuates the serum cortisol response to exogenous adrenocorticotropin. 300 53

Previous studies have shown that hypoglycemia may reduce counterregulatory responses to subsequent hypoglycemia in healthy subjects and in patients with diabetes. The effect of hypoglycemia on the hormonal response to a nonhypoglycemic stimulus is uncertain. To test the hypothesis that the cortisol response to corticotropin (ACTH) infusion is independent of antecedent hypoglycemia, 10 healthy subjects received a standard ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] intravenously over 240 minutes) at 8:00 AM on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00 AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03 and 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects also had paired control studies in random order during which a 330-minute euglycemic clamp (mean glucose, 5.0 +/- 0.11 mmol/L) instead of a hypoglycemic clamp was performed on day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol (435 +/- 46 v 317 +/- 40 nmol/L, P < .02) both decreased from day 1 to day 3 following intervening hypoglycemia. In contrast, with intervening euglycemia, neither basal ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/- 38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC) for the cortisol response to successive ACTH infusions was increased (4,734 +/- 428 nmol/L over 240 minutes [day 3] v 3,526 +/- 434 nmol/L over 240 minutes [day 1], P < .01). The maximum incremental cortisol response was also significantly increased (805 +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with interval euglycemia (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3,709 +/- 391 nmol/L over 240 minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3] v 592 +/- 85 nmol/L [day 1] were unchanged. Following exposure to intermittent hypoglycemia in healthy humans, fasting morning ACTH and cortisol levels are reduced and the incremental cortisol response to an infusion of ACTH is enhanced. The enhanced cortisol response to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal gland by endogenous ACTH produced during the hypoglycemia. These data suggest that adrenal function testing by exogenous ACTH administration is not impaired by prior exposure to hypoglycemia. Moreover, the reduced cortisol response to recurrent hypoglycemia in patients with well-controlled diabetes is not likely the result of impaired adrenal responsiveness.
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PMID:Recurrent hypoglycemia does not impair the cortisol response to adrenocorticotropin infusion in healthy humans. 978 30