A novel functional estrogen receptor on human sperm membrane interferes with progesterone effects

We have identified an estrogen receptor of approximately 29 kDa apparent mo lecular weight in human sperm membranes by ligand and Western blot analysis , respectively, using peroxidase-conjugated E-2 and an antibody directed ag ainst the ligand binding region of the genomic receptor (alpha H222). Such receptor is functional since 17 beta E-2 induces a rapid and sustained incr ease of intracellular calcium concentrations ([Ca2+](i)) which is completel y eliminated by preincubation with alpha H222. 17 beta E-2 effects on calci um are clearly mediated by a membrane receptor, as they are reproduced by t he membrane-impermeable conjugate of the hormone BSA-E-2. Dose-response cur ve for this effect is biphasic with EC(50)s in the nanomolar and micromolar range. In addition to calcium increase, 17 beta E-2 stimulates tyrosine ph osphorylation of several sperm proteins including the 29-kDa protein band. Preincubation of human sperm with 17 beta E-2 inhibits calcium and acrosome reaction increases in response to progesterone. We conclude that estrogens may play a role in the modulation of non-genomic action of progesterone (P ) in human sperm during the process of fertilization. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.