title: Regulation of the proliferation and differentiation of Leydig stem cells in the adult testis.
abstract: We reported previously that stem cells associated with adult rat testis seminiferous tubules are able to give rise to differentiated Leydig cells in vitro. The regulatory mechanisms by which they do so, however, are uncertain. Herein, we hypothesized that the proliferation and differentiation of Leydig cell stem cells (stem Leydig cells, SLCs) depend upon locally produced factors from the seminiferous tubules. Microarray analysis revealed that platelet-derived growth factor receptor alpha (PDGFRalpha) is up-regulated and PDGFRbeta is down-regulated with postnatal differentiation of SLCs. This suggested that their ligands, PDGF-AA and PDGF-BB, respectively, might have important roles in SLC proliferation and differentiation. To test this, we developed a unique in vitro culture system in which SLCs proliferate on the surfaces of cultured seminiferous tubules largely during Week 1 of culture and their progeny subsequently differentiate to testosterone-forming Leydig cells during Weeks 2 through 4. Using this system, seminiferous tubules from adult rat testes were cultured with PDGF-AA or PDGF-BB for up to 4 wk. Both ligands stimulated SLC proliferation during the first week of culture, with PDGF-BB significantly more potent than PDGF-AA. Furthermore, PDGF-AA had a stimulatory effect on SLC differentiation from Weeks 2 through 4 of culture. In contrast, PDGF-BB, which stimulated cell proliferation during Week 1, had a significant inhibitory effect on differentiation during Weeks 2 through 4. These findings, made possible by the development of the seminiferous tubule culture system, reveal distinct roles by locally produced PDGFs in SLC regulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Hana M
authors.initials: HM
authors.lastname: Odeh
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Colin
authors.initials: C
authors.lastname: Kleinguetl
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Zirkin
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China hchen@jhsph.edu.
authors.forename: Haolin
authors.initials: H
authors.lastname: Chen
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011914:Rats, Inbred BN; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000166:cytology; D013739:Testosterone / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D013739:Testosterone; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Leydig cells; PDGF; stem cells; testosterone
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