Insights into the Regulation on Proliferation and Differentiation of Stem Leydig Cells

Male hypogonadism is a clinical syndrome caused by testosterone deficiency. Hypogonadism can be caused by testicular disease (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism). The present strategy for treating hypogonadism is the administration of exogenous testosterone. But exogenous testosterone is reported to have negative side effects including adverse cardiovascular events and disruption of physiological spermatogenesis probably due to its inability to mimic the physiological circadian rhythm of testosterone secretion in vivo. In recent years, a growing number of articles demonstrated that stem Leydig cells (SLCs) can not only differentiate into functional Leydig cells (LCs) in vivo to replace chemically disrupted LCs, but also secrete testosterone in a physiological pattern. The proliferation and differentiation of SLCs are regulated by various factors. However, the mechanisms involved in regulating the development of SLCs remain to be summarized. Factors involved in the regulation of SLCs can be divided into environmental pollutants, growth factors, cytokine and hormones. Environmental pollutants such as Perfluorooctanoic acid (PFOA) and Triphenyltin (TPT) could suppress SLCs proliferation or differentiation. Growth factors including FGF1, FGF16, NGF and activin A are essential for the maintenance of SLCs self-renewal and differentiation. Interleukin 6 family could inhibit differentiation of SLCs. Among hormones, dexamethasone suppresses SLCs differentiation, while aldosterone suppresses their proliferation. The present review focuses on new progress about factors regulating SLC's proliferation and differentiation which will undoubtedly deepen our insights into SLCs and help make better clinical use of them. Different factors affect on the proliferation and differentiation of stem Leydig cells. Firstly, each rat was intraperitoneally injected EDS so as to deplete Leydig cells from the adult testis. Secondly, the CD51+ or CD90+ cells from the testis of rats are SLCs, and the p75+ cells from human adult testes are human SLCs. These SLCs in the testis start to proliferate and some of them differentiate into LCs. Thirdly, during the SLCs regeneration period, researchers could explore different function of those factors (pollutants, growth factors, cytokines and hormones) towards SLCs.