Testosterone processing by pituitary cells in culture: an examination of the role of 5 alpha-reduction in androgen action on the gonadotroph.
Dispersed rat pituitary cells were exposed to [1,2,6,7-3H]testosterone ([3H]T, 10(-8) M) to assess the role of 5 alpha-reduction in T regulation of gonadotroph secretion. After 4 to 48 hours of exposure, [3H]T metabolites isolated by thin-layer chromatography were characterized in medium and cell homogenates as well as bound to androgen receptors salt-extracted from purified nuclear pellets. Receptor-bound 5 alpha-[3H]dihydrotestosterone ([3H]DHT)/total [3H]androgens rose progressively from 16% at 4 hours to more than 50% at 48 hours. Coincubation with 4-MA (10- to 1,000-fold molar excess) or testosterone-17 beta-carboxylic acid (TCA; 1,000-fold excess) reduced receptor-bound [3H]DHT/[3H]androgen to less than 10% and 20%, respectively, but elevated [3H]T-receptor levels. Despite inhibiting 5 alpha-reductase activity, TCA and 4-MA had no effect on T suppression of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion or T enhancement of total (cell + secreted) follicle-stimulating hormone levels. The results suggest that 5 alpha-reduction to DHT is not essential for the expression of the direct influences of T on gonadotropin synthesis and secretion in rat gonadotrophs.
Kamel
F
F
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Krey
L C
LC
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D011374:Progesterone; C020509:testosterone 17 beta-carboxylic acid; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006493:Heparin; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase