Effects of the insulin-like growth factor system on testicular differentiation and function: a review of the literature.

We recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans. In animals, IGF1/IGF1R has been found to be involved in testicular development during embryogenesis, in Sertoli cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation. Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular volume. The molecular pathways responsible for testicular differentiation and IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF system may be involved in FSH signaling also in humans. We suggest a possible molecular pathway occurring in human SCs, which involves both IGF1 and FSH through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH-induced effects may open new ways for a targeted therapy in idiopathic non-FSH-responder oligoasthenoteratozoospermia.