Although, progesterone has been undoubtedly recognized as a female steroid hormone it is recently reported to regulate two vital processes in male reproduction viz spermatogenesis and sperm acrosome reaction. My laboratory is interested in defining the mechanisms by which progesterone acts in male system Our studies for the first time demonstrated that nuclear progesterone receptors (PR) are expressed in the germ cells of human testis in a stage specific manner indicting that that PR may have a regulatory role in spermatogenesis. By cDNA arrays we did demonstrate significant alternations in gene expression profiles in response to progesterone challenge to mouse testicular cells providing the first definitive evidence of testis as a direct site for progesterone actions.
In addition to the nuclear receptors, my group is also involved in identification of the sperm membrane PR. Using an immuno-proteomics approach, we have identified the sperm membrane PR protein, which is christened as Progesterone Receptor on Acrosomal Membrane (PRAM). PRAM is a distinct entity from its nuclear PR as it localizes integrally on the sperm acrosomal membrane. We have cloned human PRAM and expressed the recombinant protein E. coli. Studies are underway to determine its steroid specificity and identify the progesterone binding domain using in silico and deletion mutation approaches. Studies are also underway to determine its putative molecular nature and the signal transduction cascades mediated via this receptor using a systems biology approach. The discovery of a new membrane steroid receptor, unrelated to nuclear receptors will provide the first plausible explanation of how steroids can initiate rapid hormonal responses in target cells by activating receptors on the cell surface.
Another area we are focusing is the role of developmental genes in adulthood. It is now recognized that several of the developmental genes expressed during organogenesis are also expressed in the adult. HOXA 10 & 11 belongs to the class of Homeobox genes that are expressed in the developing uterus and are reported to be important for endometrial receptivity and embryo implantation. As a part of our endeavor to understand the molecular basis of implantation in humans, a project is undertaken to repress HOXA 10 using RNAi probes in human endometrial cells and identify the changes in gene ex-pression profiles by microarrays. It is expected that these investigations may help in improving our basic understanding of the molecular physiology of endometrial receptivity and implantation. It is also envisaged that these studies may also have broad clinical implications such as in diagnosis and management of infertility and contraceptive development.