The Regulation of the Proliferation and Differentiation of Rat Leydig Cell Precursor Cells After EDS Administration or Daily HCG Treatment

Teerds, K. J.; Rooij, Dirk G. de; Rommerts, F. F. G.; Wensing, C. J. G.

doi:10.1002/j.1939-4640.1988.tb01061.x

Cited by 106 publications

(74 citation statements)

References 27 publications

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“…However, there is evidence that although the Leydig cell number is relatively stable, there is some turnover. For example, 3 H-thymidine has been shown to be incorporated into cells in the interstitial compartment (27), and injections of rats with high doses of hCG to result in the formation of new Leydig cells (28). These early studies, based on 3 H-thymidine labeling, in fact may have underestimated the turnover rate of adult Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Wang

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

197

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Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

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Section: Discussionmentioning

confidence: 99%

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Wang

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

197

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“…EDS was administered in a single dose of 75 mg͞kg body weight. This treatment resulted in a rapid elimination of the LCs present in the adult testis by 4 days after treatment (46). Approximately 1,000,000 SLCs in a 25-l volume of PBS were injected into the parenchyma of recipient testes 4 days after the rats had received EDS.…”

Section: Methodsmentioning

confidence: 99%

In search of rat stem Leydig cells: Identification, isolation, and lineage-specific development

Dong

Sottas

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

240

301

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Leydig cells (LCs) are thought to differentiate from spindle-shaped precursor cells that exhibit some aspects of differentiated function, including 3␤-hydroxysteroid dehydrogenase (3␤HSD) activity. The precursor cells ultimately derive from undifferentiated stem LCs (SLCs), which are postulated to be present in testes before the onset of precursor cell differentiation. We searched for cells in the neonatal rat testis with the abilities to: (i) proliferate and expand indefinitely in vitro (self renew); (ii) differentiate (i.e., 3␤HSD and ultimately synthesize testosterone); and (iii) when transplanted into host rat testes, colonize the interstitium and subsequently differentiate in vivo. At 1 week postpartum, spindle-shaped cells were seen in the testicular interstitium that differed from the precursor cells in that they were 3␤HSD-negative, luteinizing hormone (LH) receptor (LHR)-negative, and platelet-derived growth factor receptor ␣ (PDGFR␣)-positive. These cells were purified from the testes of 1-week-old rats. The cells contained proteins known to be involved in LC development, including GATA4, c-kit receptor, and leukemia inhibitory factor receptor. The putative SLCs expanded over the course of 6 months while remaining undifferentiated. When treated in media that contained thyroid hormone, insulin-like growth factor I, and LH, 40% of the putative SLCs came to express 3␤HSD and to synthesize testosterone. When transplanted into host rat testes from which LCs had been eliminated, the putative SLCs colonized the interstitium and subsequently expressed 3␤HSD, demonstrating their ability to differentiate in vivo. We conclude that these cells are likely to be the sought-after SLCs.c-kit ͉ leukemia inhibitory factor ͉ platelet-derived growth factor receptor ␣ ͉ puberty ͉ steroidogenesis L eydig cells (LCs) are the primary source of testosterone in the male, and their differentiation in the testes during puberty is a signature event in the development of the male body plan. It is hypothesized, but far from proven, that LCs first arise from undifferentiated stem cells [stem LCs (SLCs)] (1-3). It has been suggested that, in rats, the putative SLCs are present in the testis at birth, and that by 11 days postpartum, at least some of their progeny express LC-specific genes and thus become committed to the LC lineage (4, 5).The committed cells subsequently undergo phased transitions through progenitor and immature stages and ultimately to terminally differentiated adult LC stage (6). In particular, progenitor LCs (PLCs) form during days 12-28 postpartum (presumably from SLCs). The PLCs proliferate and also exhibit some aspects of differentiated function, including 3␤-hydroxysteroid dehydrogenase (3␤HSD) activity (7). Luteinizing hormone (LH) receptors (LHRs) first appear as the PLCs differentiate, suggesting that SLCs are likely to be independent of LH control (8). The development of the steroidogenic capacity of PLCs requires stimulation by LH (9). The mitotic activity of PLCs gradually is reduced, and the cells enlarge...

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“…Cell counts were carried out [16]. Briefly, nuclei of Leydig cells were counted; these were recognized by their more or less spherical nucleus with a typical distribution of heterochromatin and blue-purple-staining cytoplasm.…”

Section: Histological Proceduresmentioning

confidence: 99%

“…Peritubular cells and perivascular cells may be the stem cells or precursor cells of the Leydig cells [2,8,9,15,161. This assumption is supported by the fact that, after the destruction of the existing population of Leydig cells by EDS or daily hCG treatment (when the proliferative activity of intersti-tial cells is greatly enhanced), most labeled interstitial cells are located peritubularly and perivascularly [16]. Hence it cannot be excluded that in the normal adult rat new Leydig cells are formed not only as a result of proliferation of existing Leydig cells but from differentiation of Leydig cell precursors.…”

Section: Cell Renewal In the Testicular Interstitial Tissue Of Normalmentioning

confidence: 99%

“…This occurs as a result of differentiation from precursor cells after the destruction of the existing Leydig cells by the cytotoxic agent ethane dimethanesulfonate (EDS) or as a result of chronic treatment with human chorionic gonadotropin (hCG) [l-3, 8, 10, 12, 13, 161. In the latter case, the rise in the number of Leydig cells after daily hCG treatment is the result of both the proliferation of Leydig cells and the development of new Leydig cells from precursor cells [16].…”

Section: Introductionmentioning

confidence: 99%

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Turnover Time of Leydig Cells and Other Interstitial Cells in Testes of Adult Rats

Teerds

Rooij

Rommerts

et al. 1989

Archives of Andrology

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The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:OO and 21:OO for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% f 0.2%), gradually increased during treatment to 1.4% f 0.3%. The percentage of labeled peritubular cells was considerably higher and increased from 1.4% f 0.1% to 3.5% f 0.4% during [3H]thymidine treatment. The remaining interstitial cells were the most actively proliferating cells: the percentage of labeled cells increased from 2.4% f 0.2% to 7.5% f 0.8% during [3H]thymidine treatment. Leydig cells, peritubular cells, and the remaining interstitial cells in the adult rat testis undergo proliferation. By means of a linear regression analysis and an arcsin transformation, an estimation of the time interval needed to replace various types of interstitial cells was obtained. Taking into account the 95 % confidence interval, the turnover time of Leydig cells ranged from 142 to 2823 days. The calculated turnover time for the peritubular cells was 85 to 257 days.

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The Regulation of the Proliferation and Differentiation of Rat Leydig Cell Precursor Cells After EDS Administration or Daily HCG Treatment

Cited by 106 publications

References 27 publications

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

In search of rat stem Leydig cells: Identification, isolation, and lineage-specific development

Turnover Time of Leydig Cells and Other Interstitial Cells in Testes of Adult Rats

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