Cell Biology of Leydig Cells in the Testis

This article reviews results on differentiation, structure, and regulation of Leydig cells in the testes of rodents and men. Two different populations—fetal and adult Leydig cells—can be recognized in rodents. The cells in these two populations are different in ultrastructure, life span, capacity for androgen synthesis, and mechanisms of regulation. A brief survey on the origin, ontogenesis, characterization of precursors, ultrastructure, and functional markers of fetal and adult Leydig cells is presented, followed by an analysis of genes in Leydig cells and the role of luteinizing hormone and its receptor, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, androgen and its receptor, anti-Müllerian hormone, estrogens, and thyroid hormones. Various growth factors modulate Leydig cell differentiation, regeneration, and steroidogenic capacity, for example, interleukin 1α, transforming growth factor β, inhibin, insulin-like growth factors I and II, vascular endothelial growth factor, and relaxin-like growth factor. Retinol and retinoic acid increase basal testosterone secretion in adult Leydig cells, but decrease it in fetal Leydig cells. Resident macrophages in the interstitial tissue of the testis are important for differentiation and function of Leydig cells. Apoptosis of Leydig cells is involved in the regulation of Leydig cell number and can be induced by cytotoxins. Characteristics of aging Leydig cells in rodents seem to be species specific. 11β-Hydroxysteroid dehydrogenase protects testosterone synthesis in the Leydig cells of stressed rats. Last, the following aspects of human Leydig cells are briefly described: origin, differentiation, triphasic development, aging changes, pathological changes, and gene mutations leading to infertlity.