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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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Nestin expression in testis during rat ontogenetic development, in nestin-GFP transgenic mice, and adult humans. (a) Immunoblots show the regulation in rat testis of CytP450, nestin, and NF-H during postnatal development. (b–d) The distribution of nestin-immunoreactive structures in rat testis at postnatal days 5 (b), 27 (c) and 90 (d) is shown. (e–g) GFP expression in testes of transgenic mice expressing GFP under the control of the nestin second-intron enhancer (green fluorescence) is detectable in Leydig cells and their vascular progenitors based on morphology (arrows point to PCs). In g, nuclei are additionally marked by DAPI (blue). (h and i) Immunohistochemical staining for nestin on adult human testis sections from individuals without (h) or with (i) Leydig cell hyperplasia. Tubular compartments (T), Leydig cells (LC), and nestin-positive vessels (arrows) are indicated. In i, stars mark the lumen of a small vessel.
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fig5: Nestin expression in testis during rat ontogenetic development, in nestin-GFP transgenic mice, and adult humans. (a) Immunoblots show the regulation in rat testis of CytP450, nestin, and NF-H during postnatal development. (b–d) The distribution of nestin-immunoreactive structures in rat testis at postnatal days 5 (b), 27 (c) and 90 (d) is shown. (e–g) GFP expression in testes of transgenic mice expressing GFP under the control of the nestin second-intron enhancer (green fluorescence) is detectable in Leydig cells and their vascular progenitors based on morphology (arrows point to PCs). In g, nuclei are additionally marked by DAPI (blue). (h and i) Immunohistochemical staining for nestin on adult human testis sections from individuals without (h) or with (i) Leydig cell hyperplasia. Tubular compartments (T), Leydig cells (LC), and nestin-positive vessels (arrows) are indicated. In i, stars mark the lumen of a small vessel.

Mentions: Next, we investigated whether the regeneration of Leydig cells after EDS treatment has similarities to the formation of a mature Leydig cell population in rats during normal postnatal development. Immunoblot analyses of Cyt P450scc revealed a biphasic expression pattern (Fig. 5 a): protein levels most significantly increase during puberty (d 24 and 27) to attain maximum (i.e., adult) values, but there is also an elevated expression at the earliest (postnatal day 5) stage examined. This developmental pattern is consistent with a gradual decrease in the number of fetal-type Leydig cells during initial postnatal development followed by the appearance and plentiful accumulation of adult-type Leydig cells (Ge et al., 1996). Comparative analyses of nestin and NF-H revealed striking similarities to the Leydig cell repopulation process after EDS treatment. Nestin expression is initially high and declines in time with the abundant emergence of (adult) Leydig cells, whereas the postnatal expression of NF-H commences later (between d 5 and 10) and peaks (around d 15) before the switch from nestin to CytP450 expression (Fig. 5 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)

Nestin expression in testis during rat ontogenetic development, in nestin-GFP transgenic mice, and adult humans. (a) Immunoblots show the regulation in rat testis of CytP450, nestin, and NF-H during postnatal development. (b–d) The distribution of nestin-immunoreactive structures in rat testis at postnatal days 5 (b), 27 (c) and 90 (d) is shown. (e–g) GFP expression in testes of transgenic mice expressing GFP under the control of the nestin second-intron enhancer (green fluorescence) is detectable in Leydig cells and their vascular progenitors based on morphology (arrows point to PCs). In g, nuclei are additionally marked by DAPI (blue). (h and i) Immunohistochemical staining for nestin on adult human testis sections from individuals without (h) or with (i) Leydig cell hyperplasia. Tubular compartments (T), Leydig cells (LC), and nestin-positive vessels (arrows) are indicated. In i, stars mark the lumen of a small vessel.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172461&req=5

fig5: Nestin expression in testis during rat ontogenetic development, in nestin-GFP transgenic mice, and adult humans. (a) Immunoblots show the regulation in rat testis of CytP450, nestin, and NF-H during postnatal development. (b–d) The distribution of nestin-immunoreactive structures in rat testis at postnatal days 5 (b), 27 (c) and 90 (d) is shown. (e–g) GFP expression in testes of transgenic mice expressing GFP under the control of the nestin second-intron enhancer (green fluorescence) is detectable in Leydig cells and their vascular progenitors based on morphology (arrows point to PCs). In g, nuclei are additionally marked by DAPI (blue). (h and i) Immunohistochemical staining for nestin on adult human testis sections from individuals without (h) or with (i) Leydig cell hyperplasia. Tubular compartments (T), Leydig cells (LC), and nestin-positive vessels (arrows) are indicated. In i, stars mark the lumen of a small vessel.
Mentions: Next, we investigated whether the regeneration of Leydig cells after EDS treatment has similarities to the formation of a mature Leydig cell population in rats during normal postnatal development. Immunoblot analyses of Cyt P450scc revealed a biphasic expression pattern (Fig. 5 a): protein levels most significantly increase during puberty (d 24 and 27) to attain maximum (i.e., adult) values, but there is also an elevated expression at the earliest (postnatal day 5) stage examined. This developmental pattern is consistent with a gradual decrease in the number of fetal-type Leydig cells during initial postnatal development followed by the appearance and plentiful accumulation of adult-type Leydig cells (Ge et al., 1996). Comparative analyses of nestin and NF-H revealed striking similarities to the Leydig cell repopulation process after EDS treatment. Nestin expression is initially high and declines in time with the abundant emergence of (adult) Leydig cells, whereas the postnatal expression of NF-H commences later (between d 5 and 10) and peaks (around d 15) before the switch from nestin to CytP450 expression (Fig. 5 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