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Progenitor cells of the testosterone-producing Leydig cells revealed.

Davidoff MS, Middendorff R, Enikolopov G, Riethmacher D, Holstein AF, Müller D - J. Cell Biol. (2004)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy, University of Hamburg, Germany. davidoff@uke.uni-hamburg.de

ABSTRACT
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.

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Neural characteristics of Leydig cells and their vascular progenitors. (a) Immunoblots show transiently elevated levels of NF-H and a reduced expression of GFAP in testis during the period of Leydig cell depletion after EDS treatment. VSMCs, but not endothelial cells (EC, marked by an arrow), are the sites of NF-H expression (b). In contrast, newly formed Leydig cells are immunoreactive for GFAP (c), GAP43 (d), TrkA (e and f), GDNF (g), and N-CAM (h). Both VSMCs (i, arrow) and PCs (j and k, arrowheads), as well as newly formed Leydig cells (k, LC), are characterized by the expression of NG2, and Leydig cells (LC) together with their vascular progenitors (VSMC, arrow; PCs, arrowheads) are sites of PDGFR-β expression (l and m). T, seminiferous tubules.
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fig4: Neural characteristics of Leydig cells and their vascular progenitors. (a) Immunoblots show transiently elevated levels of NF-H and a reduced expression of GFAP in testis during the period of Leydig cell depletion after EDS treatment. VSMCs, but not endothelial cells (EC, marked by an arrow), are the sites of NF-H expression (b). In contrast, newly formed Leydig cells are immunoreactive for GFAP (c), GAP43 (d), TrkA (e and f), GDNF (g), and N-CAM (h). Both VSMCs (i, arrow) and PCs (j and k, arrowheads), as well as newly formed Leydig cells (k, LC), are characterized by the expression of NG2, and Leydig cells (LC) together with their vascular progenitors (VSMC, arrow; PCs, arrowheads) are sites of PDGFR-β expression (l and m). T, seminiferous tubules.

Mentions: Next, we examined intermediate filament proteins that are expressed subsequent to nestin in cells of the nervous system during their differentiation into the neuronal/glial lineage (Dahlstrand et al., 1995; Doetsch, 2003). These studies revealed a conspicuous regulation of neurofilament-H (NF-H). Its expression in testis increases (first detectable at d 7) later than that of nestin (d 1, see Fig. 2 a) and is sustained at high levels for a relatively short time (around d 14) after EDS exposure (Fig. 4 a). Thus, transiently elevated expression of NF-H, localized to the vascular Leydig cell progenitors (Fig. 4 b), coincides with their transition from proliferative to transformation activity.


Progenitor cells of the testosterone-producing Leydig cells revealed.

Davidoff MS, Middendorff R, Enikolopov G, Riethmacher D, Holstein AF, Müller D - J. Cell Biol. (2004)

Neural characteristics of Leydig cells and their vascular progenitors. (a) Immunoblots show transiently elevated levels of NF-H and a reduced expression of GFAP in testis during the period of Leydig cell depletion after EDS treatment. VSMCs, but not endothelial cells (EC, marked by an arrow), are the sites of NF-H expression (b). In contrast, newly formed Leydig cells are immunoreactive for GFAP (c), GAP43 (d), TrkA (e and f), GDNF (g), and N-CAM (h). Both VSMCs (i, arrow) and PCs (j and k, arrowheads), as well as newly formed Leydig cells (k, LC), are characterized by the expression of NG2, and Leydig cells (LC) together with their vascular progenitors (VSMC, arrow; PCs, arrowheads) are sites of PDGFR-β expression (l and m). T, seminiferous tubules.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172461&req=5

fig4: Neural characteristics of Leydig cells and their vascular progenitors. (a) Immunoblots show transiently elevated levels of NF-H and a reduced expression of GFAP in testis during the period of Leydig cell depletion after EDS treatment. VSMCs, but not endothelial cells (EC, marked by an arrow), are the sites of NF-H expression (b). In contrast, newly formed Leydig cells are immunoreactive for GFAP (c), GAP43 (d), TrkA (e and f), GDNF (g), and N-CAM (h). Both VSMCs (i, arrow) and PCs (j and k, arrowheads), as well as newly formed Leydig cells (k, LC), are characterized by the expression of NG2, and Leydig cells (LC) together with their vascular progenitors (VSMC, arrow; PCs, arrowheads) are sites of PDGFR-β expression (l and m). T, seminiferous tubules.
Mentions: Next, we examined intermediate filament proteins that are expressed subsequent to nestin in cells of the nervous system during their differentiation into the neuronal/glial lineage (Dahlstrand et al., 1995; Doetsch, 2003). These studies revealed a conspicuous regulation of neurofilament-H (NF-H). Its expression in testis increases (first detectable at d 7) later than that of nestin (d 1, see Fig. 2 a) and is sustained at high levels for a relatively short time (around d 14) after EDS exposure (Fig. 4 a). Thus, transiently elevated expression of NF-H, localized to the vascular Leydig cell progenitors (Fig. 4 b), coincides with their transition from proliferative to transformation activity.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy, University of Hamburg, Germany. davidoff@uke.uni-hamburg.de

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus