Inhibition of rat granulosa cell differentiation by overexpression of Gαq

摘要

Activation of FSH and LH receptors in undifferentiated granulosa cells (i.e., no prior exposure to FSH) results in comparable induction of progesterone production, but activation of the LH receptor is less effective than FSH in inducing aromatase and the native LH receptor. Because the LH receptor can also activate the Gαq signaling pathway, we investigated whether activation of this pathway could be responsible for these differences. Overexpression of Gαq inhibited FSH induction of both the estradiol and progesterone biosynthetic pathways as well as mRNA levels for cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), LH receptor (LHr), and P450aromatase (aromatase). This suppression was associated with a reduction (P < 0.05) in FSH-stimulated cAMP production. Lower cAMP levels were not due to reduced FSH receptor (FSHr) mRNA levels or reduced levels of Gαs. Phosphodiesterase (PDE) activity and regulator of G-protein signaling 2 (RGS2) mRNA levels were significantly (P < 0.05) increased by Gαq, both of which could account for diminished cAMP levels. We conclude that Gαq signaling pathway inhibits both estradiol and progesterone production comparably and thus activation of this pathway does not seem to account for differences between FSH and LH in the regulation of aromatase and the LH receptor.