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Relative importance of 5alpha reduction for the androgenic and LH-inhibiting activities of delta-4-3-ketosteroids.
Steroids 1977 March
The significance of 5alpha reduction of c19, delta1,4-3-ketosteroids in regulating growth of the rat ventral prostate (VP) was examined. The androgenic and LH-inhibiting activities of a C19 delta1,4-3-detosteroid which does not undergo appreciable 5alpha reduction were compared with those of its 5alpha reduced analogue and those of testosterone (T). In intact rats M (17beta-hydroxy-17alpha-methyl-androsta-1:4-dien-3-one) caused a suppression of VP weights and plasma testosterone concentrations, and in castrated rats suppressed plasma LH concentrations. M was considerably less androgenic and moderately less potent as an inhibitor of LH secretion than either T or the 5alpha reduced analogue of M [17beta-hydroxy-17alpha-methyl-5alpha-androst-1-ene-3-one; (5alphaM)]. 5alphaM was found to be at least as androgenic and as active as an inhibitor of LH as T, suggesting that the weak activity of M may be attributable to a lack of reduction to 5alphaM. Following incubation of 3H-M with VP minces, over 96% of the radioactivity recovered corresponded with M by TLC. Under identical conditions 32-48% of the radioactivity recovered from incubations with 14C-T corresponded with 5alpha reduced metabolites of T. This study demonstrates the importance of 5alpha reduction for both the androgenic and LH-inhibiting activities of delta4-3-ketosteroids.
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