Current understanding of adult stem cells in Leydig cell biology

Adult Leydig cells (ALCs) are specialized androgen-producing cells that originate from stem Leydig cells (SLCs) during pubertal development. SLCs reside in the testicular interstitial compartment, either centrally or near peritubular myoid cells and vasculature. While their precise origin remains under investigation, prevailing evidence suggests SLCs derive from mesonephros-derived mesenchymal cells, though contributions from neural crest or coelomic epithelium lineages have been proposed. Luteinizing hormone (LH) is a critical regulator of Leydig cell maturation and steroidogenic function, yet the mechanisms enabling SLCs to acquire responsiveness to LH/growth factor signals remain incompletely characterized. Current models suggest paracrine factors from Sertoli cells, peritubular myoid cells, immune cells, or germ cells may orchestrate the early SLC-to-Leydig cell transition prior to LH sensitivity. Fetal Leydig cell-derived androgens may also prime ALC development. Postnatally, LH signaling drives both proliferative expansion (yielding ∼25 million Leydig cells in adult rats) and terminal differentiation of intermediate progenitor stages, ultimately establishing the testosterone-secreting ALC population essential for male reproductive function.