Steroid receptors typically are ligand-dependent transcription factors that modulate expression of specific genes by binding to promoter elements. However, steroid hormones also appear to bind to membrane-associated receptors to induce rapid activation of signal transduction pathways in the absence of changes in gene transcription. Progesterone is believed to act through such receptors to activate Xenopus oocyte maturation and to rapidly stimulate calcium influx and chloride efflux to trigger the acrosome reaction in human sperm. These receptors have not been identified, but a cDNA believed to encode a porcine membrane-associated progesterone receptor (MAPR) has been reported recently. We have cloned the homologous mouse cDNA and used it and antisera to two deduced peptide sequences that it encodes to determine the distribution of the transcript and protein in the male reproductive system. A 1.8 kb transcript is abundant in mouse testis, isolated germ cells and epididymis. The protein is present in spermatogenic cells (pachytene spermatocytes and spermatids) and Leydig cells in the testis, in epithelial cells lining the epididymis, and associated with anterior acrosome of spermatozoa. However, MAPR lacks sequence homology to steroid-binding proteins, calcium channel proteins, or tyrosine kinases. The porcine cDNA encoded a component of a progesterone-binding complex and we hypothesize that other proteins in the complex provide these functions. This hypothesis is being tested with a yeast two-hybrid screening approach, using MAPR as the bait to identify other proteins that associate with this component.
