Rapid signaling responses in Sertoli cell membranes induced by follicle stimulating hormone and testosterone: calcium inflow and electrophysiological changes.

This minireview describes the rapid signaling actions of follicle stimulating hormone (FSH) and testosterone in immature Sertoli cells mainly related to Ca(2+) inflow and the electrophysiological changes produced by hormones. The rapid membrane actions of FSH occur in a time frame of seconds to minutes, which include membrane depolarization and the stimulation of (45)Ca(2+) uptake. These effects can be prevented by pertussis toxin (PTX), suggesting that they are likely mediated by Gi-protein coupled receptor activation. Furthermore, these effects were inhibited by verapamil, a blocker of the L-type voltage-dependent Ca(2+) channel (VDCC). Finally, FSH stimulation of (45)Ca(2+) uptake was inhibited by the (phosphoinositide 3-kinase) PI3K inhibitor wortmannin. These results suggest that the rapid action of FSH on L-type Ca(2+) channel activity in Sertoli cells from pre-pubertal rats is mediated by the Gi/Gβγ/PI3Kγ pathway, independent of its effects on insulin-like growth factor type I (IGF-I). Testosterone depolarizes the membrane potential and increases the resistance and the (45)Ca(2+) uptake in Sertoli cells of the seminiferous tubules of immature rats. These actions were nullified by diazoxide (K(+)(ATP) channel opener). Testosterone actions were blocked by both PTX and the phospholipase C (PLC) inhibitor U73122, suggesting the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP2) hydrolysis via the Gq protein in the testosterone-mediated pathway. These results indicate that testosterone acts on the Sertoli cell membrane through the K(+)(ATP) channels and PLC-PIP2 hydrolysis, which closes the channel, depolarizes the membrane and stimulates (45)Ca(2+) uptake. These results demonstrate the existence of rapid non-classical pathways in immature Sertoli cells regulated by FSH and testosterone.