Modulation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase by follicle-stimulating hormone

Follicle-stimulating hormone (FSH) is a glycoprotein that transmits its signals via a G protein-coupled receptor. As yet, not many targets of FSH have been identified, able to justify the critical role of this hormone on reproductive events. On the other hand, among the biological activities of the endocannabinoid anandamide (AEA), growing interest has been attracted by the regulation of mammalian fertility. Recently, we have shown that treatment of mouse primary Sertoli cells with FSH enhances the activity of the AEA hydrolase (fatty acid amide hydrolase, FAAH), whereas it does not affect the enzymes that synthesize AEA, nor the level of the AEA-binding type-2 cannabinoid and type-1 vanilloid receptors. In addition, diacylglycerol lipase and monoacylglycerol lipase, which, respectively, synthesize and degrade the other major endocannabinoid 2-arachidonoylglycerol, were not regulated by FSH. Interestingly, FAAH stimulation by FSH occurred through protein kinase A and aromatase-dependent pathways that were able to modulate FAAH activity (via phosphorylation of accessory proteins) and faah gene expression (via an estrogen response element on the promoter region). Taken together, these data identify FAAH as the only target of FSH among the elements of the endocannabinoid system, with a critical impact on Sertoli cell proliferation, and thus spermatogenesis and male reproduction.