Direct Effects of Medroxyprogesterone Acetate on Testes: Possible Mechanisms Examined by Testicular Perfusion

The uptake of ³H‐testosterone by the nuclear androgen receptor of rat testis was studied using a perfusion system which was adapted for the simultaneous perfusion of 8 testes. Following perfusion with ³H‐testosterone, the major nuclear steroid in the testis of hypophysectomized rats was testosterone rather than one of its 5α‐metabolites. The accumulation of ³H‐testosterone in testicular nuclei was saturable, inhibited by perfusion with excess testosterone or 4 progestins (including medroxyprogesterone acetate, MPA) which are known to bind to the androgen receptor. Saturation of testicular androgen receptors with ³H‐MPA could not be demonstrated due to the high non‐specific binding of this non‐polar steroid. However, specific binding of ³H‐MPA was demonstrated by fractionation of salt‐extractable testicular nuclear receptor on sucrose gradients. Perfused rat testes were also used to examine the direct effects of MPA on testosterone secretion. When testes were perfused with MPA, 20 μg/ml (but not 1 μg/ml) both basal and hCG induced testosterone secretion were inhibited 30 % and 60 %, respectively. In conclusion, MPA could exert a direct effect on testis via the androgen receptor as it docs in other androgen responsive tissues. Another direct effect of this progestin on the testis could be by inhibiting testosterone secretion. 7his response requires high levels of MPA in the perfusion medium suggesting that this might be a pharmacological effect of this pregestin.