INVOLVEMENT OF TYROSINE PROTEIN PHOSPHATASES (PTP) IN STEROIDOGENESIS.

C.PAZ, F.COMEJO MACIEL, M.V.GUASTAVINO, C.PODEROSO AND E.J.PODESTÁ

Quebec, Canada

Congreso; X International Congress on Hormonal Steroids; 1998

Protein phosphorylation is an integral component of signal transduction pathways within eukariotic cells and is regulated by the fine interplay of protein kinases and phosphatases.. Protein phosphorylation by cAMP-dependent protein kinase is a major and well described mechanism in lutropin/chorionic gonadotropin (LH/CG) or adrenocorticotropín (ACTH) action in adrenal zona fasciculata (ZF) and Leydig (L) cells. However, very littIe is known about the role of protein phosphatases in this mechanism, particularly about the functional role of PTPs. The aim of the present work was to study the involvement of PTPs in the acute regulation of steroidogenesis in ZF and L cells. Phenylarsine oxide (PAO), a permeable inhibitor of PTP activity; significantly reduced ACTH- and CG-stimulated steroidogenesis: ACTH (1 nM) 16.2± 2.5 vs. ACTH + PAO (2 nM) 9.3±1.0 ng/corticosterone/105 ZF cells, p<0.001; CG (1 mU/ml) 18.3±0.6 vs. CG + PAO (2.5 mM) 3.5 ±0.3 ng testosterone/106 L cells, p < 0.001. PAO had no effect on basal or.22ROH cholesterol supported steroidogenesis. Similar effects were also detectad with pervanadate, other PTP inhibitor. Increased activity of PTP was detectad in cytosols obtained from adrenal glands stimulated in vivo with ACTH or in vitro with both ACTH and 8BrcAMP usíng RCM-Iysozyme as substrate, and by immuno detection of endogenous phosphoproteins using antiphosphotyrosine antibodies. We report for the first time, the activation of PTPs in hormone-stimulated steroidogenesis, suggesting a cross talk between Ser/Tre and Tyr phosphorylation pathways.