Steroid specificity of the human sperm membrane progesterone receptor

The aim of this study was to evaluate the effect of several abeopregnane, steroidal heterocycles (A/B-transandrostano [2,3-d]isoxazole, and 17-spiroandrostano[2,3-c]furazan), and 6 alpha, 11 beta, 16 alpha-trisubstituted 19-nor-pregnadienedione on the influx of extracellular Ca2+ in human sperm. These steroidal compounds had minimal genomic progestational, androgenic, oi estrogenic activity with the exception of 16 alpha-ethyl-6 alpha-methyl-11 beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione which was four times more progestational than progesterone. Some of the steroidal compounds, e.g., 16 alpha-ethyl-6 alpha-methyl-11 beta-(4-N,N-dimethylaminophenyl)-19-nor-pregna-4,9-diene-3,20-dione and 2',3',4',5'-tetrahydrospiro[furan-2'beta,17-androstano] [2,3-c]furazan produced an influx of Ca2+ into human spermatozoa. These studies indicate that high (10 mu M) concentrations of certain steroidal compounds are selective for the sperm membrane progesterone receptor; since most of them have minimal genomic activity. The steroidal compounds that elicited an influx of Ca2+ caused an initial high influx but were not as potent as progesterone, since no effects were observed below 1 mu M, whereas progesterone at 1 mu M produced a maximum effect. Progesterone as well as the steroidal compounds caused a modest increase in the number of acrosome-reacted spermatozoa. Molecular modeling revealed that 5 alpha-dihydro-2,3-fused and 4,4-dimethyl-5-ene-2,3-fused steroidal heterocycles possessing different conformations compared to that of progesterone are responsible for elevation of Ca2+. In conclusion, a unique, non-genomic progesterone receptor is present on human spermatozoa and several steroidal compounds that do not have progestational effects may activate this sperm membrane receptor, resulting in Ca2+ influx.