Inhibition of Luteinizing Hormone (LH)-Releasing Hormone-Induced Secretion of LH in Rat Anterior Pituitary Cell Culture by Testosterone without Conversion to 5α-Dihydrotestosterone

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Abstract
The role of 5.alpha.-reduction of testosterone in the inhibition of LH [luteinizing hormone] secretion was investigated in rat anterior pituitary cell cultures. Pituitary cells were preincubated with testosterone or dihydrotestosterone (17.beta.-hydroxy-5.alpha.-androstan-3-one) for 17 h and then with LHRH for an additional 4 h. Dihydrotestosterone was 6-fold more potent than testosterone in the inhibition of LHRH-induced LH release. Basal LH secretion was not affected by either androgen. The inhibition curves of testosterone and dihydrotestosterone were not shifted by the presence of the 5.alpha.-reductase inhibitors 17.beta.-N,N-diethylcarbamoyl-4-methyl-4-aza-5.alpha.-androstan-3-one (4-MA) and 17.beta.-N,N-diisopropylcarbamoyl-4-aza-androstan-3-one (DIPA). Neither 4-MA nor DIPA alone had an effect on either basal or LHRH-induced LH release. When pituitary cells were incubated with [3H]testosterone for 17 h, the radioactivities were unmetabolized testosterone (66.9 .+-. 2.4%), dihydrotestosterone (13.3 .+-. 0.5%), androstenedione (15.9 .+-. 1.3%), 5.alpha.-androstane-3,17-dione (2.8 .+-. 0.3%) and 3.alpha.(.beta.),17.beta.-androstanediol (< 1%). In the presence of 4-MA or DIPA, 5.alpha.-reduction of testosterone was completely inhibited; androstenedione was the only metabolite. Androstenedione was only 12% as potent as testosterone in the inhibition of LHRH stimulation of LH release, and conversion of [3H]androstenedione to testosterone and dihydrotestosterone did occur in these cells. When [3H]dihydrotestosterone was incubated with pituitary cells, the radioactivities were dihydrotestosterone (64.4 .+-. 0%), 5.alpha.-androstanedione (19.3 .+-. 1%), 3.alpha.(.beta.),17.beta.-androstanediol (7.7 .+-. 1.7%), and unknown polar metabolites. 4-MA and DIPA had no effect on the metabolism of dihydrotestosterone. Both testosterone and dihydrotestosterone inhibit LHRH-induced LH release, and this activity of testosterone does not depend on its 5.alpha.-reduction.