AN AUTOCRINE PROGESTERONE POSITIVE FEEDBACK LOOP MEDIATES OXYTOCIN UP-REGULATION IN BOVINE GRANULOSA-CELLS DURING LUTEINIZATION

During luteinization of bovine granulosa cells in vitro in the presenc e of insulin, or insulin plus forskolin, there is a massive upregulati on not only of progesterone production, but also of the gene for the p eptide hormone oxytocin, with secretion of the peptide into the medium . By using the progesterone receptor antagonists, RU486 or onapristone , we have shown that this upregulation of the oxytocin gene is mediate d by an autocrine loop involving endogenous progesterone and the proge sterone receptor in the granulosa cells. The inhibition of oxytocin ge ne expression by the anti-gestagens can be reversed by medroxyprogeste rone acetate but not by dexamethasone, showing that the effect is due to the endogenous progesterone. Since oxytocin also appears to be invo lved in a positive feedback loop regulating steroid output, these resu lts show that endogenous progesterone itself is a key feedback element in the cascade of events termed luteinization, and that possibly anti -gestagens can influence ovarian function in vivo by directly disrupti ng this process.