Abstract: 3

FSH-INDUCED DOWN-REGULATION OF THE FSHR GENE IN SERTOLI CELLS INVOLVES REPRESSIVE CHROMATIN STRUCTURE.

Walter Tribley^{1 *}, Jeong-Seon Kim^{1 *}, Michael Griswold^{1 *}
Department of Biochemistry, Washington State University, Pullman, WA 99164-4660 ¹

FSH is required for normal spermatogenesis. In males, FSH signalling is regulated by controlling the number of FSH receptors (FSHR) in Sertoli cells that are competent to bind FSH and transduce a signal to the cytosol. After FSH-induced signal transduction in rat Sertoli cells, transcription of the gene for FSHR is shut off. The hypothesis that the FSHR gene is silenced by the inducible cAMP early repressor (ICER) was tested. Electrophoretic mobility shift assay, using nuclear proteins from FSH-treated Sertoli cells and an oligonucleotide probe containing the putative ICER binding site within the FSHR promoter, was used to determine the identity of the nuclear proteins that bind to that site and their relative affinity for the site. A major complex containing cFos and a minor complex containing ICER were formed. The expression of transiently-transfected reporter gene constructs controlled by the FSHR promoter in rat Sertoli cells was measured and evaluated in FSH-treated cells relative to untreated cells. No FSH-induced repression was observed. Given that FSH-induced repression and cell-specific expression is only observed when the gene is stably integrated in chromatin, the hypothesis that FSH-induced repression involves chromatin structure was tested. Treatment of Sertoli cells with the histone deacetylase inhibitor trichostatin A completely de-repressed the FSHR gene in Sertoli cells treated with FSH. These data support the hypothesis that chromatin structure is involved in repressing transcription of the FSHR gene. NIH R37HD10808 to MDG

    This abstract is being presented on Saturday, July 31 at 2:00 PM at Todd 116.