Oduwole Olayiwola O, Peltoketo Hellevi, Huhtaniemi Ilpo T
Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
Cancer and Translational Medicine Research Unit, Laboratory of Cancer Genetics and Tumor Biology, Biocenter Oulu, University of Oulu, Oulu, Finland.
Front Endocrinol (Lausanne). 2018 Dec 14;9:763. doi: 10.3389/fendo.2018.00763. eCollection 2018.
Spermatogenesis is a concerted sequence of events during maturation of spermatogonia into spermatozoa. The process involves differential gene-expression and cell-cell interplay regulated by the key endocrine stimuli, i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-stimulated testosterone. FSH affects independently and in concert with testosterone, the proliferation, maturation and function of the supporting Sertoli cells that produce regulatory signals and nutrients for the maintenance of developing germ cells. Rodents are able to complete spermatogenesis without FSH stimulus, but its deficiency significantly decreases sperm quantity. Men carrying loss-of-function mutation in the gene encoding the ligand () or its receptor ( present, respectively, with azoospermia or suppressed spermatogenesis. Recently, the importance of high intratesticular testosterone concentration for spermatogenesis has been questioned. It was established that it can be completed at minimal intratesticular concentration of the hormone. Furthermore, we recently demonstrated that very robust constitutive FSHR action can rescue spermatogenesis and fertility of mice even when the testosterone stimulus is completely blocked. The clinical relevance of these findings concerns a new strategy of high-dose FSH in treatment of spermatogenic failure.
精子发生是精原细胞成熟为精子过程中一系列协同发生的事件。该过程涉及由关键内分泌刺激（即促卵泡激素（FSH）和黄体生成素（LH）刺激的睾酮）调节的差异基因表达和细胞间相互作用。FSH独立且协同睾酮影响支持性睾丸支持细胞的增殖、成熟和功能，这些细胞产生调节信号和营养物质以维持发育中的生殖细胞。啮齿动物能够在没有FSH刺激的情况下完成精子发生，但其缺乏会显著降低精子数量。携带编码配体（）或其受体（）的基因功能丧失突变的男性分别表现为无精子症或精子发生受抑制。最近，睾丸内高浓度睾酮对精子发生的重要性受到质疑。已确定在最低睾丸内激素浓度下也可完成精子发生。此外，我们最近证明，即使睾酮刺激完全被阻断，非常强大的组成型FSHR作用也可以挽救小鼠的精子发生和生育能力。这些发现的临床意义涉及高剂量FSH治疗生精功能衰竭的新策略。
