title: Cell surface-binding sites for progesterone mediate calcium uptake in human sperm.
abstract: Recent studies (e.g. Blackmore, P. F., Beebe, S. J., Danforth, D. R., and Alexander, N.) (1990) J. Biol. Chem. 265, 1376-1380) have shown that in human sperm, progesterone produces a rapid increase in intracellular free calcium ([Ca2+]i) and an induction of the acrosome reaction (e.g. Osman, R. A., Andria, M. L., Jones, A. D., and Meizel, S. (1989) Biochem, Biophys. Res. Commun. 160, 828-833). In this study, the location of progesterone receptors on the cell surface of human sperm was identified using progesterone immobilized on bovine serum albumin (BSA) (progesterone 3-(O-carboxymethyl)oxime:BSA) as well as progesterone and its 3-O-carboxymethyloxime derivative. Using fluorescence microscopy, BSA-fluorescein isothiocyanate was shown to be excluded from intact sperm, thus validating the use of progesterone 3-(O-carboxymethyl)oxime:BSA to identify cell surface-binding sites for progesterone. The immobilized progesterone and the 3-O-carboxymethyloxime derivative rapidly increased [Ca2+]i and were full agonists, although they were approximately 1.5 orders of magnitude less potent than progesterone. They also displayed an identical time course to increase [Ca2+]i as free progesterone, and the entire increase in [Ca2+]i was due to the influx of Ca2+. This progesterone-mediated response displayed different steroid receptor characteristics since the very potent inhibitors of genomic progesterone responses, RU38486 and ZK98.299, were very ineffective at inhibiting the progesterone-mediated increase in [Ca2+]i. Also the synthetic progestins megestrol, medroxyprogesterone acetate, norgestrel, norethynodrel, norethindrone, R5020, and cyproterone acetate did not mimic the effects of progesterone to increase [Ca2+]i. It is proposed that a distinct nongenomic cell surface receptor for progesterone exists in human sperm.
authors.affiliation: Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
authors.forename: P F
authors.initials: PF
authors.lastname: Blackmore
authors.forename: J
authors.initials: J
authors.lastname: Neulen
authors.forename: F
authors.initials: F
authors.lastname: Lattanzio
authors.forename: S J
authors.initials: SJ
authors.lastname: Beebe
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002606:Charcoal / Q000494:pharmacology; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D004533:Egtazic Acid; D006067:Gonanes / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D009640:Norethindrone / Q000494:pharmacology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012710:Serum Albumin, Bovine; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D006067:Gonanes; D011980:Receptors, Progesterone; D002606:Charcoal; D012710:Serum Albumin, Bovine; D011374:Progesterone; D017373:Cyproterone Acetate; D004533:Egtazic Acid; D007811:Lanthanum; D003534:Cyproterone; C053238:onapristone; D002118:Calcium; D009640:Norethindrone