Action of steroids and plant triterpenoids on CatSper Ca2+ channels in human sperm

Abstract

The sperm-specific Ca2+ channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration and, thereby, the swimming behavior of sperm. Human CatSper is activated by progesterone (1, 2), an oviductal hormone, which stimulates Ca2+ influx and motility responses. By patch-clamp recording from human sperm, Mannowetz et al. (3) studied the action of the steroids pregnenolone sulfate (pregS), testosterone, hydrocortisone, and 17-β-estradiol (estradiol) as well as that of the plant triterpenoids pristimerin and lupeol on CatSper currents. Here, we report data that contradict most of these results. We agree with Mannowetz et al. (3) that pregS activates CatSper, and that pregS and progesterone use the same binding site. We also observe that pregS enhances CatSper currents (Fig. 1 E and G ); moreover, we show that pregS evokes a rapid Ca2+ influx (Fig. 1 A , C , and D ) and that human sperm (from a patient with deafness-infertility syndrome) that lack CatSper do not respond to pregS (Fig. 1 B ). Using Ca2+ fluorimetry, we and others showed by cross-desensitization experiments that progesterone and its derivatives (e.g., 17-OH-progesterone) employ the same binding site to activate CatSper (1, 4). Similarly, sequential application of progesterone and pregS (and vice versa) leads to cross-desensitization (Fig. 1 J and K ), confirming … [↵][1]3To whom correspondence should be addressed. Email: timo.struenker{at}ukmuenster.de. [1]: #xref-corresp-1-1