Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid hormone production within the gonads and adrenals requires a continuous supply of cholesterol derived from de novo synthesis within the gland and from uptake of circulating plasma lipoproteins. Steroid hormone secretion was prospectively studied over 24 months in 64 hypercholesterolemic subjects (group I, aged 52 +/- 1 years [mean +/- SEM], 61% male) participating in a randomized double-blind clinical trial of pravastatin (20 to 80 mg daily), a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, compared with patients taking cholestyramine or other lipid-lowering drugs (group II). Attempts were made in both groups to maintain serum low-density lipoprotein cholesterol (LDL-C) levels between the 25th and 50th percentile for age and gender. At 24 months, serum LDL-C level decreased by 42% +/- 3% in group I and 44% +/- 1% in group II (P < .001 v baseline, NS between groups). Basal secretion of cortisol, aldosterone, and dehydroepiandrostenedione sulfate (DHEA-S) was maintained throughout the study. However, the serum DHEA-S secretory response to Cortrosyn (Organon, West Orange, NJ) diminished in both treatment groups at 6 and 12 months (P < .05). In men, basal serum testosterone levels and the testosterone response to human chorionic gonadotropin (HCG) did not change. There was some diminution of sperm motility noted in both treatment groups at 6 and 12 months in the subset of men undergoing semen analysis (n = 14, P < .05). In conclusion, pravastatin had no significant effect on steroid metabolism. Changes noted in DHEA-S were not specific for pravastatin, suggesting that this impairment is related to lipid-lowering effects.
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PMID:Long-term endocrine function in hypercholesterolemic patients treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. 841 67

New therapeutic indications of the antiprogesterone RU 486 are emerging which require long-term administration and raise the question of its safety because of the associated antiglucocorticoid action of the drug. A trial was designed to assess the antiglucocorticoid effect of RU 486, possible manifestations of peripheral cortisol deprivation, and the adrenocortical and corticotrophin reserves. Ten normal males were given RU 486 per os (200 mg/day) or placebo between 0800-0900 h for eight days in a randomized, double-blind, crossover design, with a 1-month interval between the two periods. RU 486 induced the overactivation of the pituitary-adrenal axis. Baseline values (mean +/- SEM) before and at end of treatment were, respectively: 0800 h plasma cortisol, 147.3 +/- 15.5 and 257.6 +/- 8.8 ng/ml; 0800 h salivary cortisol, 5.8 +/- 1.2 and 15.2 +/- 0.8 ng/ml; nocturnal (2200-0800 h) urinary cortisol, 8.4 +/- 1.5 and 33.7 +/- 11.1 micrograms; and 0800 h plasma ACTH, 29.2 +/- 3.7 and 60.2 +/- 8.4 pg/ml. All of these variations were different from those during placebo treatment (0.0001 < p < .03) and disappeared four days after the end of treatment. A daily record of subjective clinical symptoms, body weight and temperature, blood pressure, and heart rate showed no side effects, and no significant variation during treatment. Blood electrolyte and eosinophil counts were unchanged; fasting blood glucose was slightly higher at the end of treatment (5.0 +/- 0.2 vs. 4.7 +/- 0.1 mmol/L; p < .04). The adrenocortical response to Cortrosyn (0.25 mg IM) was exaggerated during RU 486 treatment (p < .006). Peak values before and at the end of treatment were, respectively: plasma cortisol, 272.5 +/- 15.2 and 347.1 +/- 20.6 ng/ml; and salivary cortisol, 17.0 +/- 2.2 and 31.1 +/- 3.1 ng/ml. Direct pituitary stimulation (100 micrograms ovine corticotrophin release hormone (CRH), followed by 1 IU LVP) also induced exaggerated corticotroph and adrenocortical responses (p < .005). Peak values before and at the end of treatment were, respectively: plasma ACTH, 147.7 +/- 24.6 and 254.0 +/- 41.3 pg/ml: and plasma cortisol, 231.6 +/- 7.3 and 319.2 +/- 12.3 ng/ml. These data show that 8-day treatment with 200 mg RU 486 daily induces a hormonally detectable antiglucocorticoid effect without clinical symptoms. This state results in a reversible cortisol overproduction and a preservation of adrenocortical and pituitary reserves.
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PMID:Pituitary-adrenal response to RU 486 in man. 926 47