THE ANTIOVULATORY ACTIVITY OF PROGESTERONE ANTAGONISTS IS NOT CORRELATED TO THEIR ANTIPROGESTATIONAL POTENCY IN THE RAT

Progesterone antagonists often differ in regard to their potency to bl ock ovulation in rats although they may possess similar (antiprogestat ional' (abortive) activity. Therefore, the questions arose as to: (a) whether antiovulatory and antiprogestational effects (on endometrial a nd mammary gland parameters) of antiprogestins correlate at all; and ( b) which mechanism(s) may be responsible for their ability to abolish ovulation. To answer these questions we set out to compare the influen ces of two progesterone antagonists, Onapristone (ON) a very potent an d ZK 136798 only a weak inhibitor of ovulation, to assess changes on t he one hand on typical progestational actions and on the other hand on factors known to regulate ovulation. For this purpose immature PMSG/h CG primed and adult female rats and infantile female rabbits were trea ted either with ON, ZK 136798 or vehicle in different treatment schedu les. In these investigations ON and ZK 136798 showed similar antiproge stational activities on the progesterone-induced development of mammar y glands (rats) and the secretory transformation of endometrium (rabbi ts). ON blocked an induced or a spontaneous ovulation, whereas ZK 1367 98 only revealed a very weak antiovulatory effect. Both ON and ZK 1367 98 stimulated basal levels of LH, estradiol, and testosterone, whereas the preovulatory LH surge was decreased to the same extent. Interesti ngly, in contrast to ZK 136798, ON reduced the preovulatory increase i n progesterone secretion. These results clearly indicate: (a) that ant iovulatory potency and antiprogestational activity may not be correlat ed in the rat; and (b) that decreased preovulatory levels of progester one following treatment with ON may play an important role in intraova rian mechanism(s) contributing to a blocking of ovulation. Copyright ( C) 1996 Elesevier Science Ltd.