Androgens inhibit plasminogen activator activity secreted by Sertoli cells in culture in a two-chambered assembly

The addition of androgens (testosterone or dihydrotestosterone) resulted in decreased levels of detectable plasminogen activator activity in the medium when Sertoli cells were maintained in culture in a serum-free chemically defined medium in a two-chambered assembly. This occurred in the presence or absence of extracellular matrix or peritubular cells in the system. In the complete two-chambered assembly, addition of androgens simultaneously resulted in a small but significant increase in the integrity of the Sertoli cell barrier separating the two chambers, as indicated by slower rates of equilibration of [3H]methoxyinulin between inner and outer chambers. These responses to steroids appeared to be androgen specific, since other steroids examined (17 beta-estradiol, progesterone, and dexamethasone) had no detectable effects on levels of plasminogen activator activities or on barrier function. We confirmed that when FSH or (Bu)2cAMP is added to stimulate plasminogen activator secretion by Sertoli cells, the integrity of the barrier is decreased, provided no antiproteases are present in the serum-free medium. Simultaneous addition of androgens inhibited these effects of (Bu)2cAMP on Sertoli cells, but did not influence the responses of Sertoli cells to FSH. We compare actions of androgens on Sertoli cells in culture under various conditions and discuss the possible physiological significance of the inhibition of plasminogen activator activity.