UNUSUAL STEROID SPECIFICITY OF THE CELL-SURFACE PROGESTERONE-RECEPTORON HUMAN SPERM

The steroid specificity of the cell surface progesterone receptor in h uman sperm was examined with the use of progesterone, testosterone, an d androstane analogues. Many compounds were shown to be more effective than progesterone at increasing intracellular free calcium concentrat ion, e.g., 2 alpha-methyl-17 beta-methoxy-5 alpha-androstan-3-one. Sev eral testosterone analogues were demonstrated to be antagonists of pro gesterone, e.g., 9(11)-dehydro-2 alpha,17 alpha-dimethyltestosterone. The synthetic potent progestigens, norethynodrel, cyproterone acetate, norethindrone, and megestrol acetate, were found to be only weak stim ulators of the sperm cell surface receptor. Furthermore, these compoun ds were shown to antagonize the effect of progesterone to elevate intr acellular free calcium concentration in sperm. It is known that proges terone and some of its analogues bind to the intracellular progesteron e nuclear receptor via the alpha-face of the steroid molecule. In star k contrast, it was concluded from the analysis of the steroid analogue s examined on human sperm in this study that intimate contact exists b etween the effective progesterone analogues and the sperm cell surface progesterone receptor across the beta-face of the steroid C/D-ring '' upper'' edge (C11, C12, and C17). Positioning of the C21 methyl group is also critical for efficacy, and recognition of the steroid A-ring s eems not to be involved.