Regulation of spermatogenesis is a remarkable process about which little is known. While circulating hormones clearly play a role in initiating and controlling this system of rapid cell differentiation, the Sertoli cell is an important mediator of molecular information traveling from the blood to the developing sperm. To date only five factors have been shown to play a definite and essential role in modulating spermatogenesis: FSH, testosterone, stem-cell factor, c-fos, and Vitamin A. Dr. Page is focusing on Vitamin A as a molecular switch for particular proto-oncogene transcription factors including fos and jun, the genes that code for components of the API complex, as well as myb, all of which are expressed in the Sertoli cell. A current model for steroid action proposes that these compounds act as master switches for gene transcription and supports the notion that retinoids, as members of the steroid/thyroid-receptor supergenefamily, can also be considered as molecular switches for regulatory cascades. Dr. Page's hypothesis is that retinoid-inducible gene transcription in the seminiferous tubules is modulated not by an alteration in a single transcription factor, such as the RAR-alpha receptor, but through regulation of a complex of multiple interacting factors including the proteins encoded by fos, jun, and myb. Under this Research Planning Grant, Dr. Page will extend her recent studies, which demonstrate the up-regulation of both jun and myb gene expression following Vitamin-A stimulation of rat Sertoli cells, by evaluating the effects of Vitamin A on c-fos mRNA using Northern-blot analysis. The levels of the protein products translated from these proto-oncogenes will be determined using Western-blot techniques as well as immunostaining of testicular tissue.
