The P50 Specialized Population Research Center described in this proposal is comprised of five research projects and four core laboratories that will perform research designed to achieve a broad understanding of testes and their two major products, germ cells and steroid hormones. The biology of newly and recently identified Sertoli cell proteins will provide the basis for evaluating seminiferous tubular function and for isolating and sequencing germ cell proteins that regulate Sertoli cells. A detailed understanding of the Sertoli cell product, androgen-binding protein (ABP), will be derived from an analysis of how individual structural changes in this protein alter its function; following alterations in the ABP cDNA, mutant ABP produced in vitro will be compared with native ABP so that the structure of this binding protein can be related to its ability to bind and activate androgen-responsive cells. Studies of the promoter regions of the B-glucuronidase and KAP genes will identify regions of interaction with androgen receptor and other transcription factors; these experiments will provide an understanding of how androgen stimulates specific genes in selected tissues. Parallel studies of the clusterin gene promoter will demonstrate how cAMP suppresses accumulation of this mRNA in Leydig and Sertoli cells; unlike the well-characterized process by which cAMP stimulates selected genes, the suppressive effect of this intracellular modulator on transcription has not been elucidated.
| Zhang, X; Jeyakumar, M; Petukhov, S et al. (1998) A nuclear receptor corepressor modulates transcriptional activity of antagonist-occupied steroid hormone receptor. Mol Endocrinol 12:513-24 |
| Phillips, D M; Lakshmi, V; Monder, C (1989) Corticosteroid 11 beta-dehydrogenase in rat testis. Endocrinology 125:209-16 |
| Phillips, D M; Goldstein, M; Zacharopoulos, V R et al. (1987) Tubules in semen of infertile patients. Case report. J Androl 8:61-3 |
| Morris, I D; Phillips, D M; Bardin, C W (1986) Ethylene dimethanesulfonate destroys Leydig cells in the rat testis. Endocrinology 118:709-19 |
