FSH and LH Stimulation of Granulosa Cell Prodynorphin Gene Expression Abolished by Overexpression of a Nonfunctional Mutant of the RI Subunit of Protein Kinase A

Abstract

At least three second-messenger systems are potentially involved in follicle stimulating hormone (FSH) activation of follicular development. They are cAMP/protein kinase A (cAMP-dependent protein kinase; PKA) (1), phosphoinositide turnover (2), and calcium/calmodulin(3); the latter two both act to increase the activity of protein kinase C. FSH has many actions on the ovary, and these three systems may be of different importance in contributing to each action of FSH. One mechanism by which FSH drives follicular development is its ability to stimulate the expression of mRNAs that encode important ovarian anabolic enzymes (4) and secretory products (5), including the endogenous opioid peptide genes prodynorphin (6) and proopiomelanocortin (7). To delineate the relative importance of different second-messenger systems in transducing the stimulatory effects of FSH on granulosa cells (GC) we tested the hypothesis that suppression of the cAMP/PKA system in these cells would alter FSH and luteinizing hormone (LH) stimulation of prodynorphin gene expression.