A new prostaglandin E receptor mediates calcium influx and acrosome reaction in human spermatozoa

Zona pellucida protein 3, a protein of the egg's extracellular matrix, and progesterone secreted by granulosa cells surrounding the oocyte are regarded as physiological stimuli of sperm acrosome reaction. Signal transduction steps initiated by both stimuli result in influx of Ca2+ from the extracellular space. Herein, we propose a role for prostaglandin (PG) E as a physiological inducer of Ca2+ influx and acrosome reaction in human spermatozoa. PGE1 specifically binds to human sperm membranes (Kd = 20.4 nM; Bmax = 88 fmol/mg protein) and induces a pertussis toxin-insensitive, transient increase in intracellular Ca2+ concentrations, which can be blocked by microM concentrations of La3+, Gd3+, and Zn2+. The kinetic profile was similar to that observed after progesterone challenge. Sequential application of both agonists did not lead to cross-desensitization. E prostaglandins were found to be the only prostanoids with agonistic properties (EC50 values for PGE1 and PGE2: <10 nM and 300 nM, respectively). Pharmacological characteristics were not compatible with those of cloned prostanoid receptors indicating the expression of a distinct membrane receptor. Activation of the sperm E prostanoid receptor stimulates incorporation of [alpha-32P]GTP azidoanilide into immunoprecipitated Galphaq/11 subunits. Thus, in human sperm, PG induces Ca2+ influx and acrosome reaction via a Gq/11-coupled E prostanoid receptor. The block of PGE1-induced Ca2+ transients and acrosome reaction by physiological Zn2+ concentrations highlights a role of Zn2+ as an endogenous Ca2+ channel blocker present in seminal plasma protecting sperm from premature PGE1-evoked increases in intracellular Ca2+ concentrations.