我们最近描述了隐睾的发生,少弱精子症,和生殖器异常患者远端15q染色体结构异常。这一观察使我们假设胰岛素样生长因子(IGF)受体(IGF1R),在15q26.3染色体带上作图,可能与睾丸功能有关。为了进一步评估这个主题,我们回顾了探索IGF系统[IGF1,IGF2,IGF1R,动物和人类睾丸水平的胰岛素受体底物(IRS)]。在动物中,已发现IGF1/IGF1R参与胚胎发育过程中的睾丸发育。在支持细胞(SC)增殖中,和生殖细胞(GS)的增殖和分化。有趣的是,IGF1R似乎通过PI3K/AKT途径介导卵泡刺激素(FSH)作用。在人类中,IGF1直接增加睾丸体积。负责睾丸分化和IGF1/IGF1R信号传导的分子途径在物种之间高度保守;因此,IGF系统也可能参与人的FSH信号传导。我们建议在人类SCs中可能发生的分子途径,通过PI3K/AKT途径涉及IGF1和FSH。承认IGF1介导FSH诱导的作用可能为特发性非FSH反应者少弱精子症的靶向治疗开辟新方法。
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.