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Published online 29 November 2004. doi:10.1083/jcb.200409107
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 5, 935-944
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Article

 Progenitor cells of the testosterone-producing Leydig cells revealed

Michail S. Davidoff1, Ralf Middendorff1,5, Grigori Enikolopov4, Dieter Riethmacher3, Adolf F. Holstein1, and Dieter Müller2

1 Institute of Anatomy, University of Hamburg, 20246 Hamburg, Germany
2 Institute for Hormone and Fertility Research, University of Hamburg, 20246 Hamburg, Germany
3 Center for Molecular Neurobiology Hamburg, University of Hamburg, 20246 Hamburg, Germany
4 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724
5 Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany

Correspondence to Michail S. Davidoff: davidoff{at}uke.uni-hamburg.de

The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair.

Abbreviations used in this paper: CNS, central nervous system; EDS, ethane dimethane sulphonate; GFAP, glial fibrillary acidic protein; NF-H, neurofilament-H; PC, pericyte; PDGFR, PDGF receptor; SMA, smooth muscle {alpha}-actin.


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