Inhibitory peptides help identify receptor complex vital to male fertility
The acrosome reaction is critical for the sperm to penetrate the female egg and fertilize it. Progesterone plays a key role in the acrosome reaction, but how this works has been unclear since spermatozoa lack classical progesterone receptors. Wenming Xu and collaborators at Sichuan University, China, The Chinese University of Hong Kong, and the Australian National University, have shown that the progesterone-induced Ca2+ influx required for the acrosome reaction involves the progesterone receptor or modulator, gamma-aminobutyric acid type A (GABAA) receptor delta subunit (GABRD), in combination with the P2X2 receptor.
The first confirmation that delta subunits were involved in the Ca2+influx came with an experiment that demonstrated that increased intracellular levels of Ca2+ in spermatozoa after progesterone stimulation were suppressed by the δ(392-422) inhibitory peptide but unaffected by a scrambled δ control peptide or a Υ2-peptide.