P2 Analysis of androgen- and TGF-beta-regulated proteins in Sertoli cells
In the testis clusterin (syn: ApoJ, Sp-40, TRPM-2, SGP-2) is involved in sperm maturation, (anti-) apoptosis, lipid transport, cell aggregation and cell adhesion. The Sertoli cells are the primary source of clusterin which can be modulated by testosterone or transforming growth factor (TGF)-betas. Extracellular clusterin enhances Sertoli cell aggregation, but the biological effects of intracellular clusterin have not been studied to date in Sertoli cells.
Secreted clusterin was found to exhibit prosurvival effects, in contrast to intracellular clusterin, which acts in a proapoptotic manner. In non-testicular cells clusterin was reported to bind to TGF-beta receptor II (TBR2), thus stabilizing TGF-beta signaling. In the present study the following aims will be addressed: 1) Analysis of androgen-regulated SC-specific proteins and their influence on germ cell (GC) differentiation or induction of meiosis in SC/GC co-culture; 2) Pathway analysis of effects of TGF-betas or testosterone on clusterin; 3) Evaluation of intra- versus extracellular clusterin on SC and GC function; 4) Association of clusterin with impaired spermatogenesis.