DIFFERENTIATION OF ADULT LEYDIG-CELLS

Adult Leydig cells originate within the testis postnatally. Their form ation is a continuous process involving gradual transformation of prog enitors into the mature cell type. Despite the gradual nature of these changes, studies of proliferation, differentiation and steroidogenic function in the rat Leydig cell led to the recognition of three distin ct developmental stages in the adult Leydig cell lineage: Leydig cell progenitors, immature Leydig cells and adult Leydig cells. In the firs t stage, Leydig cell progenitors arise from active proliferation of me senchymal-like stem cells in the testicular interstitium during the th ird week of postnatal life and are recognizable by the presence of Ley dig cell markers such as histochemical staining for 3 beta-hydroxyster oid dehydrogenase (3 beta-HSD) and the present of luteinizing hormone (LH) receptors. They proliferate actively and by day 28 postpartum dif ferentiate into immature Leydig cells. In the second stage, immature L eydig cells are morphologically recognizable as Leydig cells. They hav e an abundant smooth endoplasmic reticulum and are steroidogenically a ctive, but primarily produce 5 alpha-reduced androgens rather than tes tosterone. Immature Leydig cells divide only once, giving rise to the total adult Leydig cell population. In the third and final stage, adul t Leydig cells are fully differentiated, primarily produce testosteron e and rarely divide. LH and androgen act together to stimulate differe ntiation of Leydig cell progenitors into immature Leydig cells. Prelim inary data indicate that insulin like growth factor-1 (IGF-1) acts sub sequently in the transformation of immature Leydig cells into adult Le ydig cells.