Rapid non-genomic actions of progesterone stimulate Ca2+ influx and the acrosome reaction in human sperm.

This review summarizes some recent findings in human sperm which show that progesterone and 17 alpha hydroxyprogesterone are able rapidly (within seconds) to elevate [Ca2+]i and elicit the acrosome reaction (AR) via a non-genomic cell surface receptor. Progesterone promotes a transient elevation in [Ca2+]i which is blocked by extracellular La3+ and Ni2+ and removal of extracellular Ca2+ following chelation with EGTA. Some studies suggest that polyamines, trypsin-like proteases, and progesterone receptor aggregation are involved in progesterone-induced Ca2+ influx and AR. The receptor is not stimulated by the potent synthetic progestigins (e.g. promegestone, norethynodrel, megestrol acetate, cyproterone acetate) and is weakly antagonized by the genomic anti-progestins RU 486 and ZK 98.299. The sedative-hypnotic 3 alpha hydroxyl A-ring reduced pregnane steroids, which are powerful activators of the GABAA Cl- channel, are weak activators of Ca2+ influx and the AR. These data suggest that human sperm have a cell surface steroid receptor which is unlike the genomic progesterone receptor and the GABAA Cl- channel steroid receptor.