title: Identification, proliferation, and differentiation of adult Leydig stem cells.
abstract: Leydig cells, the testosterone-producing cells of the adult testis, rarely turn over. However, their elimination with ethane dimethanesulfonate (EDS) is followed by the appearance of new, fully functional adult Leydig cells. The cells that give rise to the new Leydig cells have not been well characterized, and little is known about the mechanism by which they are regulated. We isolated cells expressing platelet-derived growth factor receptor-α, but not 3β-hydroxysteroid dehydrogenase (3β-HSD(neg)) from the testes of EDS-treated adult rats. Depending on conditions, these cells proliferated indefinitely or differentiated and produced testosterone. To localize these cells and to determine the effect of the testicular environment on their function, the seminiferous tubules and testicular interstitium were physically separated and cultured. During the first 72 h in culture, 3β-HSD(neg) cells on the tubule surfaces underwent divisions. Some of these cells later expressed 3β-HSD and produced testosterone. Removal of the newly formed 3β-HSD(pos) cells from the tubule surfaces with EDS, followed by further culture of the stripped tubules, resulted in the reappearance of testosterone-producing cells. These results, taken together, suggest that the precursors for newly formed Leydig cells are stem cells, with many if not all situated on the surfaces of the seminiferous tubules. Although normally quiescent, the stem cells are capable of self-renewal and differentiation. The development of the tubule culture system should provide a valuable in vitro approach to assess the role(s) of niche components on the function of adult Leydig stem cells despite their residing in a complex mammalian tissue.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Stanley
authors.forename: Chieh-Yin
authors.initials: CY
authors.lastname: Lin
authors.forename: Shiying
authors.initials: S
authors.lastname: Jin
authors.forename: June
authors.initials: J
authors.lastname: Liu
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Sottas
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
authors.forename: Barry R
authors.initials: BR
authors.lastname: Zirkin
authors.forename: Haolin
authors.initials: H
authors.lastname: Chen
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D007985:Leydig Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D013739:Testosterone; D007986:Luteinizing Hormone