Population Council Research that makes a difference

Leydig cells in the testes are the primary source of testosterone in the male. The chief tropic stimulus of testosterone secretion is luteinizing hormone (LH, a pituitary hormone). Population Council researchers are developing procedures for purifying the stem cells of Leydig cells using the testes of perinatal rats as source material. The goal of this work is to test the ability of Leydig stem cells to undergo differentiation and acquire steroidogenic capacity when transplanted back into the testis. If successful, this would provide a more physiological means of androgen replacement as a therapeutic intervention for hypogonadal boys or older men suffering from age-related declines in testosterone levels.

Researchers hypothesize that this can be done autologously (that is, with the patient furnishing his own Leydig stem cells) based on a strategy of amplifying stem cell numbers from a biopsy sample and selecting for Leydig stem cells using preparative cell sorting. A cell surface marker such as Kit receptor is one candidate for Leydig stem cells under investigation.

Previous Population Council studies established three intermediate stages of the Leydig cell lineage in rats: a mesenchymal-like, highly proliferative progenitor Leydig cell (PLC), first observed at day 10–11 postpartum that is recognized as steroidogenic; an immature Leydig cell (ILC) that has mitochondrial and smooth endoplasmic reticulum membrane structure typical of steroid-secreting cells but that synthesizes primarily 5α-reduced androgens rather than testosterone as end products; and an adult Leydig cell (ALC) that is proliferatively quiescent and terminally differentiated for testosterone secretion. The fundamental unanswered question is whether the ultimate source of adult Leydig cells is a small pool of undifferentiated, self-renewing stem Leydig cells (SLCs).