Nongenomic progesterone receptor on human spermatozoa: biochemical aspectsand clinical implications

Progesterone (P) is a physiological stimulus of human sperm functions. It i s present in high levels at the site of fertilization (cumulus oophorus) an d has been described to affect several sperm functions, including motility, capacitation, acrosome reaction, and the ability to bind and to respond to zona proteins. The effects of the steroid are mediated essentially by an i ncrease of intracellular calcium concentrations, stimulation of activity of phospholipases, phosphorylation of proteins, efflux of chloride. These eff ects are due to activation of a rapid, nongenomic pathway. Whether the effe cts of progesterone are mediated or not by specific interactions with sperm membrane proteins is questioned. By using an antibody directed against the C-terminal region (P-binding region) of the genomic receptor, we have rece ntly identified two sperm proteins with molecular weights distinct from the classic genomic receptors. In addition, ligand blot analysis with peroxida se-conjugated P demonstrated that P specifically binds these two proteins. Classical ligand binding experiments demonstrated the presence of two speci fic binding sites with affinity in the nanomolar and in the micromolar rang e, respectively. The involvement of progesterone in the physiological proce ss leading to fertilization of the oocyte is suggested by several studies. In particular, the demonstration that sperm responsiveness to progesterone is impaired in subfertile patients and that is strictly correlated to the a bility of fertilizing the oocyte represents a further indication of the par ticipation of the steroid in this process. In addition, the determination o f sperm responsiveness may be predictive of fertilizing ability with a posi tive predictive value of 90% and can be clinically useful for the prelimina ry assessment of the male partner to select the appropriate assisted reprod uctive technique. (C) 1999 Elsevier Science Inc. All rights reserved.