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 block ovulation in rats although they may possess similar 'antiprogestational' (abortive) activity. Therefore, the questions arose as to: (a) whether antiovulatory and antiprogestational effects (on endometrial and 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 influences of two progesterone antagonists, Onapristone (ON) a very potent and ZK 136798 only a weak inhibitor of ovulation, to assess changes on the one hand on typical progestational actions and on the other hand on factors known to regulate ovulation. For this purpose immature PMSG/hCG primed and adult female rats and infantile female rabbits were treated either with ON, ZK 136798 or vehicle in different treatment schedules. In these investigations ON and ZK 136798 showed similar antiprogestational activities on the progesterone-induced development of mammary glands (rats) and the secretory transformation of endometrium (rabbits). ON blocked an induced or a spontaneous ovulation, whereas ZK 136798 only revealed a very weak antiovulatory effect. Both ON and ZK 136798 stimulated basal levels of LH, estradiol, and testosterone, whereas the preovulatory LH surge was decreased to the same extent. Interestingly, in contrast to ZK 136798, ON reduced the preovulatory increase in progesterone secretion. These results clearly indicate: (a) that antiovulatory potency and antiprogestational activity may not be correlated in the rat; and (b) that decreased preovulatory levels of progesterone following treatment with ON may play an important role in intraovarian mechanism(s) contributing to a blocking of ovulation.
Schubert
C
C
Medical University of Lübeck, Institute of Anatomy, Germany.
Donath
J
J
Michna
H
H
Nishino
Y
Y
D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004717:Endometrium / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D004971:Estrus / Q000187:drug effects; D005260:Female; D006067:Gonanes / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects*; D010062:Ovulation Induction; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013739:Testosterone / Q000378:metabolism
D000736:Androstenes; D006067:Gonanes; D006727:Hormone Antagonists; C104064:ZK 136798; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; C053238:onapristone