Effect of N-acetylsphingosine (C2) and the ceramidase inhibitor (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol on the regulation of Sertoli cell function

In the present study, a possible role of ceramide in the regulation of Sert oli cell function was investigated. Intracellular ceramide levels were incr eased by addingN-acetylsphingosine (C2) or by inhibiting ceramidase with (1 S,2R)-D-erythro-2-(N-myristoylamino)-1 -phenyl-1-propanol (MAPP). Cultured Sertoli cells were stimulated for 3 days with different doses of C2, MAPP, and their corresponding inactive analogs. The effect of these drugs was eva luated along four well-known Sertoli cell parameters: lactate and transferr in secretion, gamma-glutamyl transpeptidase (gamma-GTP) activity, and estra diol production. C2 and MAPP increased lactate production and decreased tra nsferrin secretion. The inactive analogs did not produce any effect. In FSH (follicle-stimulating hormone)-stimulated cultures, C2 and MAPP produced a further increment in lactate production and decreased FSH-stimulated trans ferrin secretion. No ef feet was observed under basal or FSH-stimulated gam ma-GTP activity, and both treatments decreased estradiol production in resp onse to FSH. Results obtained in dbcAMP (dibutyryladenosine 3':5'-cyclic mo nophosphate)-stimulated cultures suggest that the observed effects of ceram ide on transferrin secretion are secondary to a decrease in cAMP production , whereas the effects of ceramide on lactate and estradiol productions are post-cAMP formation regulatory events. In summary, our results show that ce ramide can regulate Sertoli cell function. Similar to what has been observe d for other signaling molecules, ceramide can interact with the FSH-depende nt pathway, but the precise steps involved in this interaction are still un known.