The effect of FSH on male germ cell survival and differentiation in vitro is mimicked by pentoxifylline but not insulin.
High concentrations of FSH have been shown to boost in-vitro differentiation of germ cells from men with normal spermatogenesis and from some patients with in-vivo maturation arrest. This study shows that the differentiation-promoting effect of FSH is connected to protection against germ cell apoptosis and that both effects can be mimicked by the intracellular cyclic AMP (cAMP)-elevating drug pentoxifylline. On the other hand, a high concentration of insulin, supposed to act at the insulin-like growth factor I receptor, did not exert any effect either on differentiation or apoptosis of germ cells in vitro. These data show that the in-vitro effects of supraphysiological concentrations of FSH on human spermatogenesis are mediated by the classical FSH signal transduction pathway involving cAMP as a second messenger. Pentoxifylline may thus be useful as an alternative means for intracellular cAMP elevation in men with high circulating FSH concentrations leading to desensitization of the FSH receptor.
Tesarik
J
J
Laboratoire d'Eylau, 55 rue Saint-Didier, 75116 Paris, France.
Mendoza
C
C
Greco
E
E
D000177:Acrosome / Q000378:metabolism; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D005640:Follicle Stimulating Hormone / Q000819:agonists / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009845:Oligospermia; D010431:Pentoxifylline / Q000494:pharmacology*; D013087:Spermatids / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000166:cytology
D007328:Insulin; D005640:Follicle Stimulating Hormone; D010431:Pentoxifylline