Our recent reports indicate that protein tyrosine phosphorylation is an obligatory component of the mechanism of action of ACTH in its stimulatory action of corticosteroid production in adrenal zona fasciculata (ZF). The role of protein tyrosine phosphatase (PTP) activity in the regulation of steroidogenesis by LH/chorionic gonadotropin (CG) was tested using cell-permeable PTP inhibitors. Thus, PTP inhibition blocks LH- and 8-bromo-cAMP-stimulated testosterone production by Leydig cells without affecting 22(R)OH-cholesterol-supported steroidogenesis, similar results to those obtained in the adrenal ZF/ACTH system, leading us to propose that PTP action is an obligatory and common step in the cascade triggered by both hormones. Then, we continued the study testing whether LH modulates PTP activity in MA-10 cells, a Leydig cell line. In this regard, we observed by an in-gel PTP assay two PTPs of 110 and 50 kDa that are activated by hormone and 8-bromo-cAMP activation of the cells. Moreover, there is a transient increase by the second messenger in total PTP activity that correlates with the higher activity displayed by the 110 and 50 kDa proteins in the in-gel assay. In accordance with these results, analysis of tyrosine phosphorylated proteins showed the LH-induced dephosphorylation of proteins of 120, 68 and 50 kDa. The results of this study indicate that PTPs play an important role in the regulation of Leydig cell functions and that there exists a cross talk between serine/threonine phosphorylation and tyrosine dephosphorylation mediated by hormone-activated cAMP-dependent protein kinase and PTPs. These results are the first evidence of PTP having a role in LH/CG-stimulated steroidogenesis.

This article has been cited by other articles:

				R. Castilla, M. Gadaleta, A. F. Castillo, A. Duarte, I. Neuman, C. Paz, F. Cornejo Maciel, and E. J. Podesta New Enzymes Involved in the Mechanism of Action of Epidermal Growth Factor in a Clonal Strain of Leydig Tumor Cells Endocrinology, July 1, 2008; 149(7): 3743 - 3752. [Abstract] [Full Text] [PDF]

				N. Martinelle, M. Holst, O. Soder, and K. Svechnikov Extracellular Signal-Regulated Kinases Are Involved in the Acute Activation of Steroidogenesis in Immature Rat Leydig Cells by Human Chorionic Gonadotropin Endocrinology, October 1, 2004; 145(10): 4629 - 4634. [Abstract] [Full Text] [PDF]

				M. B. Sewer and M. R. Waterman cAMP-dependent Protein Kinase Enhances CYP17 Transcription via MKP-1 Activation in H295R Human Adrenocortical Cells J. Biol. Chem., February 28, 2003; 278(10): 8106 - 8111. [Abstract] [Full Text] [PDF]