Regulation of expression of A-kinase anchoring proteins in rat granulosa cells.

FSH action on granulosa cells involves the generation of cAMP and subsequent activation of the cAMP-dependent protein kinase (PKA). The PKA holoenzyme is targeted to specific subcellular sites through the interaction of the regulatory subunits with A-kinase anchoring proteins (AKAPs). We previously reported that FSH regulates expression of AKAPs. In this report we examine the relationship between AKAP expression and cell shape. Granulosa cells cultured in the absence of FSH tend to spread and flatten. Cell spreading is accompanied by an increased expression of a 140-kDa AKAP. This spreading/flattening phenotype is independent of the specific extracellular matrix proteins (fibronectin, polylysine, and gelatin) on which cells are plated. Addition of FSH prevents both cell spreading and induction of AKAP 140. Culturing cells on poly (2-hydroxyethyl methacrylate), a surface-coating agent that inhibits cell spreading and adhesion, also inhibits expression of AKAP 140. Addition of phorbol myristate acetate, an agent known to antagonize FSH actions, blocks FSH regulation of both cell shape and AKAP 140 expression. Addition of dexamethasone plus FSH causes a synergistic increase in progesterone levels but has no effect on cell shape or induction of AKAP 140. Dexamethasone produces a dose-dependent increase in AKAP 80 expression, which is blocked by FSH, suggesting cross talk between the glucocorticoid and FSH receptor signaling pathways. These data suggest that expression of AKAP 140 is linked to regulation of cell shape, and that changes in the expression of AKAPs are regulated by several different signaling pathways.