INVIVO ANDROGEN BINDING IN RAT SKELETAL AND PERINEAL MUSCLES

In vivo binding of [3H]testosterone), [3H]5α-dihydrotestosterone and [3H]3α-androstanediol to cytosolic and nuclear fractions of LA/BC and thigh muscles has been studied in functionally hepatectomized castrated rats following a 1 h infusion of the labelled steroid. The identification of metabolites formed from each steroid has also been determined in tissue cytosols. In each experiment, ventral prostate was used as reference target tissue. After [3H]testosterone and [3H]5α-dihydrotestosterone perfusions, cytosolic binding could be demonstrated in a 8-10S peak on sucrose gradient with LA/BC and ventral prostate or in the macromolecular fraction after filtration through Sephadex G-25 with thigh muscles. In both types of muscles, [3H]-5α-dihydrotestosterone binding represented only one tenth of [3H]testosterone binding. This behaviour seems to be related to the high rate of 5α-dihydrotestosterone metabolism observed in these tissues; testosterone, on the contrary, was not metabolized. After [3H]3α-androstanediol perfusion, cytosolic [3H]androgen binding in LA/BC and in thigh muscles was almost non-existent. In muscles [3H]3α-androstanediol remained essentially unconverted. In ventral prostate, with every hormone studied level of cytosolic binding was comparable. It was observed that in this tissue [3H]testosterone and [3H]3α-androstanediol were metabolized into [3H]5α-dihydrotestosterone. Androgen binding to 0.4 M KCl extracted nuclear proteins has been demonstrated in ventral prostate as a 3.5-4.5S binding peak on sucrose gradient and this with each steroid perfused in LA/BC, only [3H]testosterone gave a well defined binding peak. In thigh muscles, levels of nuclear binding were too low to be determined. In summary, these results suggest that rat perineal and skeletal muscles possess cytosolic androgen binding proteins similar to those found in ventral prostate. However, it appears that steroid metabolism is quite different in ventral prostate and muscles with respect to presence of 5α-reductase activity and extent of conversion of 5α-dihydrotestosterone into androstanediols. These differences may explain why, in vivo, muscles bind testosterone instead of 5α-dihydrotestosterone as in ventral prostate.