Testosterone inhibition of LRH-induced luteinizing hormone release by cultures of rat anterior pituitary cells: effect of inhibitors of steroid 5 alpha reductase.
Cultures of rat anterior pituitary cells were utilized to examine the role of 5 alpha reduction in the inhibitory action of testosterone on LRH-induced LH release. Cultures were pre-treated with steroids for 48 h and then incubated 6 h with steroids plus 5 x 10(-10) M LRH, the approximate EC50 for LH and FSH release. Testosterone inhibited LRH-induced LH release with an IC50 of approximately 2 x 10(-10) M. However, even relatively high concentrations of testosterone did not completely inhibit LRH-induced release. Testosterone (and dihydrotestosterone) appeared to antagonize LRH-induced LH release but did not markedly affect 48 h basal release or LH synthesis as judged by the quantity of LH released plus that remaining intracellularly. Progesterone (10(-6) M) and heparin (1000 U/ml) were used as inhibitors of anterior pituitary steroid 4 alpha reductase. Progesterone, when combined with testosterone, markedly shifted the testosterone inhibition curve to the right (approximately 340-fold) but did not shift the dihydrotestosterone inhibition curve. Heparin also slightly shifted the testosterone inhibition curve (approximately 2.4-fold) to the right. These observations support the hypothesis that the mechanism of action of testosterone on the anterior pituitary involves 5 alpha reduction.
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology*
D058891:5-alpha Reductase Inhibitors; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006493:Heparin; D010088:Oxidoreductases