PROGESTERONE AND RU486 - OPPOSING EFFECTS ON HUMAN SPERM

Progesterone induced a rapid influx of calcium in capacitated human sp erm, followed by a long-lasting, dose-dependent increase of intracellu lar free calcium. Thereafter, progesterone increased the fraction of h yperactivated sperm and the acrosome reaction. On the contrary, the pr ogesterone antagonist RU486 (mifepristone) induced an immediate and tr ansient, dose-dependent decrease of intracellular free calcium and a d rop in the values of sperm movement parameters related to hyperactivat ion. Moreover, RU486 counteracted the effects of progesterone on calci um influx, lateral sperm head displacement, and the acrosome reaction. Therefore, RU486 effects were opposite to those of progester-one one, The nature of the membrane receptor(s) involved is unknown. Several s teroids bearing 11 beta-phenyl substitutions, with different pharmacol ogical profiles, were also investigated. It was concluded that the ste roid structure and chemical groups added to the 11 beta-phenyl influen ce effects on calcium influx.