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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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Reappearance of Leydig cells after EDS treatment. Leydig (CytP450-immunoreactive) cells are first detectable near blood vessels (arrows) in the form of clusters (a) or as single spindle-shaped cells (b) in testes 14 d after EDS. The cluster (white arrow) and spindle-shaped cell (black arrow) magnified in a and b, respectively, are indicated in c. The accumulation of Leydig cells at d 21 (d) and d 30 (e) after EDS, distributed around (d) and between (e) seminiferous tubules, is shown.
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fig1: Reappearance of Leydig cells after EDS treatment. Leydig (CytP450-immunoreactive) cells are first detectable near blood vessels (arrows) in the form of clusters (a) or as single spindle-shaped cells (b) in testes 14 d after EDS. The cluster (white arrow) and spindle-shaped cell (black arrow) magnified in a and b, respectively, are indicated in c. The accumulation of Leydig cells at d 21 (d) and d 30 (e) after EDS, distributed around (d) and between (e) seminiferous tubules, is shown.

Mentions: To prove and document reliably the known fate of Leydig cells in the rat testis after a single i.p. EDS injection, we monitored the expression of a Leydig cell marker protein, cytochrome P450 side chain cleavage enzyme (CytP450), representing the rate-limiting enzyme of steroidogenesis. CytP450-immunoreactive cells completely disappeared 3 d after EDS treatment and began to reappear ∼14 d after EDS treatment, detectable primarily as cell clusters located in the vicinity of intertubular vessels (Fig. 1 a) and in form of single, peritubularly distributed spindle-shaped cells (Fig. 1 b). At this time, the total amount of Leydig cells is still very low (Fig. 1 c), and the expression of CytP450 is not yet detectable by immunoblotting (see Fig. 2 a).


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)

Reappearance of Leydig cells after EDS treatment. Leydig (CytP450-immunoreactive) cells are first detectable near blood vessels (arrows) in the form of clusters (a) or as single spindle-shaped cells (b) in testes 14 d after EDS. The cluster (white arrow) and spindle-shaped cell (black arrow) magnified in a and b, respectively, are indicated in c. The accumulation of Leydig cells at d 21 (d) and d 30 (e) after EDS, distributed around (d) and between (e) seminiferous tubules, is shown.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Reappearance of Leydig cells after EDS treatment. Leydig (CytP450-immunoreactive) cells are first detectable near blood vessels (arrows) in the form of clusters (a) or as single spindle-shaped cells (b) in testes 14 d after EDS. The cluster (white arrow) and spindle-shaped cell (black arrow) magnified in a and b, respectively, are indicated in c. The accumulation of Leydig cells at d 21 (d) and d 30 (e) after EDS, distributed around (d) and between (e) seminiferous tubules, is shown.
Mentions: To prove and document reliably the known fate of Leydig cells in the rat testis after a single i.p. EDS injection, we monitored the expression of a Leydig cell marker protein, cytochrome P450 side chain cleavage enzyme (CytP450), representing the rate-limiting enzyme of steroidogenesis. CytP450-immunoreactive cells completely disappeared 3 d after EDS treatment and began to reappear ∼14 d after EDS treatment, detectable primarily as cell clusters located in the vicinity of intertubular vessels (Fig. 1 a) and in form of single, peritubularly distributed spindle-shaped cells (Fig. 1 b). At this time, the total amount of Leydig cells is still very low (Fig. 1 c), and the expression of CytP450 is not yet detectable by immunoblotting (see Fig. 2 a).

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