The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis

The response of granulosa cells to luteinizing hormone (LH) and follicle-st imulating hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) s ignaling. Notably, the activity of the extracellular signal-regulated kinas e (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced stero idogenesis in two granulosa derived cell lines, rLHR-4 and rFSHR-17, respec tively. We found that stimulation of these cells with the appropriate gonad otropin induced ERK activation as well as progesterone production downstrea m of PKA. Inhibition of ERR activity enhanced gonadotropin-stimulated proge sterone production, which was correlated with increased expression of the s teroidogenic acute regulatory protein (StAR), a key regulator of progestero ne synthesis. Therefore, it is likely that gonadotropin-stimulated progeste rone formation is regulated by a pathway that includes PKA and StAR, and th is process is down-regulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis but also activates down-regulation machinery i nvolving the ERR cascade. The activation of ERK by gonadotropins as well as by other agents may be a key mechanism for the modulation of gonadotropin- induced steroidogenesis.