Figure 1.

Gonadotropins trigger multiple signals that regulate steroidogenesis. LH-induced activation of the LH receptor on theca, and likely mural granulosa, cells triggers several signaling pathways that can regulate steroid production. Gα_s-mediated increases in cAMP lead to elevated PKA activity, which in turn can increase StAR and CYP17 expression and activity via mechanisms that are still not well understood. Concomitant Gβγ-mediated signaling can activate the Src/Ras/MAPK signaling cascade, which in turn has been shown to both increase and decrease StAR and CYP17 activity, depending upon the cell culture system. Of note, LH-induced Gβγ and possibly Gq signaling can also trigger PLC activation, which may affect steroidogenesis (not shown). Finally, through yet unknown mechanisms, LH receptor signaling can trigger activation of MMPs, which in turn may cleave membrane-EGF moieties to release soluble EGFs (possibly amphiregulin, epiregulin, and/or HB-EGF). These soluble EGFs can then activate the EGF receptor on granulosa, and possibly theca, cells to increase StAR activity via mechanisms that have yet to be characterized. Finally, similar to the LH receptor, activation of the FSH receptor on granulosa cells increases intracellular cAMP and activates PKA, which in turn can increase StAR and CYP19 (aromatase) expression and activity.