scholarly journals Leydig Cell Loss and Spermatogenic Arrest in Platelet-Derived Growth Factor (Pdgf)-a–Deficient Mice

2000 ◽  
Vol 149 (5) ◽  
pp. 1019-1026 ◽  
Author(s):  
Lucio Gnessi ◽  
Sabrina Basciani ◽  
Stefania Mariani ◽  
Mario Arizzi ◽  
Giovanni Spera ◽  
...  
Keyword(s):  
Growth Factor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Lineage ◽  
Cell Loss ◽  
Platelet Derived Growth Factor ◽  
Developmental Expression ◽  
Gonad Differentiation ◽  
Testicular Size ◽  
Deficient Mice

Platelet-derived growth factor (PDGF)- A–deficient male mice were found to develop progressive reduction of testicular size, Leydig cells loss, and spermatogenic arrest. In normal mice, the PDGF-A and PDGF-Rα expression pattern showed positive cells in the seminiferous epithelium and in interstitial mesenchymal cells, respectively. The testicular defects seen in PDGF-A−/− mice, combined with the normal developmental expression of PDGF-A and PDGF-Rα, indicate that through an epithelial-mesenchymal signaling, the PDGF-A gene is essential for the development of the Leydig cell lineage. These findings suggest that PDGF-A may play a role in the cascade of genes involved in male gonad differentiation. The Leydig cell loss and the spermatogenic impairment in the mutant mice are reminiscent of cases of testicular failure in man.

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

2016 ◽  
Vol 113 (10) ◽  
pp. 2666-2671 ◽  
Author(s):  
Xiaoheng Li ◽  
Zhao Wang ◽  
Zhenming Jiang ◽  
Jingjing Guo ◽  
Yuxi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Lineage ◽  
Seminiferous Tubules ◽  
Paracrine Factors ◽  
Adult Testis ◽  
Adult Leydig Cells ◽  
Neonatal Testis

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.

scholarly journals Human Testicular Peritubular Cells Host Putative Stem Leydig Cells With Steroidogenic Capacity

2014 ◽  
Vol 99 (7) ◽  
pp. E1227-E1235 ◽  
Author(s):  
Luise Landreh ◽  
Katrin Spinnler ◽  
Kerstin Schubert ◽  
Merja R. Häkkinen ◽  
Seppo Auriola ◽  
...  
Keyword(s):  
Growth Factor ◽  
Leydig Cell ◽  
Regulatory Protein ◽  
Cell Lineage ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Steroidogenic Acute Regulatory Protein ◽  
Rt Pcr ◽  
Steroidogenic Acute Regulatory ◽  
Peritubular Cells

Aim: We aim to examine the steroidogenic phenotype and the differentiation potential of human testicular peritubular cells (HTPCs) and to explore their possible relationship to the adult Leydig cell lineage. Background: The cells of the adult Leydig cell lineage may reside in the peritubular compartment of the testis. This suggestion is supported by the facts that the rodent peritubular cells can be differentiated toward this lineage and that cAMP enhances their steroidogenic potential. Methods: Human testicular biopsies, and derived HTPCs, were analyzed by immunohistochemistry, RT-PCR, and Western blotting. After stimulation by forskolin or platelet-derived growth factor-BB, quantitative RT-PCR was used to compare the levels of mRNAs encoding proteins involved in steroidogenesis and steroid production was analyzed by liquid chromatography and tandem mass spectrometry. Results: Immunohistochemical analysis revealed that the peritubular cells that form the outer part of the tubular wall express platelet derived growth factor receptor-α. Furthermore, the pluripotency markers (POU domain class 5 transcription factor 1, GATA-binding protein 4), stem Leydig cell markers (platelet derived growth factor receptor-A, leukemia inhibitory factor receptor), and mRNAs encoding proteins involved in steroidogenesis (nuclear receptor subfamily 5, group A, member 1; steroidogenic acute regulatory protein; CYP11A1; CYP17A1; 3β-hydroxysteroid dehydrogenase) were expressed by the HTPCs. Stimulation with forskolin increased the expression of the steroidogenic markers, which was accompanied by the production of pregnenolone and progesterone by HTPCs in vitro. Treatment with platelet-derived growth factor-BB induced expression of steroidogenic acute regulatory protein. Conclusions: Our results indicate that the tubular wall of the human testis is a reservoir for cells of the adult Leydig cell lineage and that the steroidogenic potential of these cells can be activated in culture.

Platelet-derived growth factor ligand and receptor subunit mRNA in the Sertoli and Leydig cells of the rat testis

1995 ◽  
Vol 108 (1-2) ◽  
pp. 155-159 ◽  
Author(s):  
Kate Lakoski Loveland ◽  
Kristina Zlatic ◽  
Alicia Stein-Oakley ◽  
Gail Risbridger ◽  
David M. deKretser
Keyword(s):  
Growth Factor ◽  
Leydig Cells ◽  
Platelet Derived Growth Factor ◽  
Receptor Subunit ◽  
Rat Testis ◽  
Subunit Mrna

Rat Leydig cells bind platelet-derived growth factor through specific receptors and produce platelet-derived growth factor-like molecules.

Endocrinology ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 2219-2224
Author(s):  
L Gnessi ◽  
A Emidi ◽  
D Farini ◽  
S Scarpa ◽  
A Modesti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Leydig Cells ◽  
Platelet Derived Growth Factor ◽  
Specific Receptors

Paracrine effects via the epidermal growth factor receptor in the rodent testis may be mediated by non-Leydig interstitial cells

1993 ◽  
Vol 136 (3) ◽  
pp. 439-NP ◽  
Author(s):  
A. Moore ◽  
I. D. Morris
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Interstitial Cell ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Thymidine Incorporation ◽  
Buoyant Density ◽  
Epidermal Growth

ABSTRACT The epidermal growth factor (EGF) receptor is expressed in a wide variety of cell types and is known to be present in the testis of many species including man. In the present study, specific 125 I-labelled EGF binding was observed in isolated interstitial cell preparations from both the intact and Leydig cell-depleted rat testis. It was demonstrated that the population of cells to which 125I-labelled EGF binds has a different buoyant density from either of the two adult Leydig cell populations, and remains unchanged in the absence of Leydig cells following in-vivo treatment with ethane dimethane sulphonate (EDS). Cells of this density (1·064 g/ml) identified by electron microscopy were fusiform mesenchymal cells, identical to those suggested by others to be able to differentiate into Leydig cells in vitro, i.e. Leydig cell precursors. In a culture system using two interstitial cell preparations of different buoyant densities from immature rats, both EGF and transforming growth factor-α (TGF-α) caused increased [3H]thymidine incorporation in the less dense cell preparation. TGF-α was more potent than EGF. EGF increased testosterone production in both fractions in amounts which could be related to the amount of 3β-hydroxysteroid dehydrogenase (3β-HSD)-positive cells. This study demonstrated that rat Leydig cells (defined as those cells which bind 125I-labelled human chorionic gonadotrophin, have distinct buoyant densities, are 3β-HSD positive and are sensitive to EDS), do not bind 125I-labelled EGF. Rather, EGF binds to a mesenchymal cell without LH receptors which is resistant to EDS. Growth factors which act via the EGF receptor increased [3H]thymidine incorporation in a Leydig cell-depleted interstitial fraction which may reflect an action upon the progenitor of the mature Leydig cell. Journal of Endocrinology (1993) 136, 439–446

scholarly journals Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Jingjing Guo ◽  
Hongyu Zhou ◽  
Zhijian Su ◽  
Bingbing Chen ◽  
Guimin Wang ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Pubertal Development ◽  
Cell Lineage ◽  
Hydroxysteroid Dehydrogenase ◽  
Mrna Levels ◽  
Steroidogenic Enzymes ◽  
Isolated Cells ◽  
Adult Leydig Cells

The objective of this study was to purify cells in the Leydig cell lineage following regeneration after ethane dimethanesulfonate (EDS) treatment and compare their steroidogenic capacity. Regenerated progenitor (RPLCs), immature (RILCs), and adult Leydig cells (RALCs) were isolated from testes 21, 28 and 56 days after EDS treatment respectively. Production rates for androgens including androsterone and 5α-androstane-17β, 3α-diol (DIOL), testosterone and androstenedione were measured in RPLCs, RILCs and RALCs in media after 3-h in vitro culture with 100 ng/ml LH. Steady-state mRNA levels of steroidogenic enzymes and their activities were measured in freshly isolated cells. Compared to adult Leydig cells (ALCs) isolated from normal 90-day-old rat testes, which primarily produce testosterone (69.73%), RPLCs and RILCs primarily produced androsterone (70.21%) and DIOL (69.79%) respectively. Leydig cells isolated from testes 56 days post-EDS showed equivalent capacity of steroidogenesis to ALCs and primarily produced testosterone (72.90%). RPLCs had cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1 and 17α-hydroxylase but had almost no detectable 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities, while RILCs had increased 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities. Because RPLCs and RILCs had higher 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase activities they produced mainly 5α-reduced androgens. Real-time PCR confirmed the similar trends for the expressions of these steroidogenic enzymes. In conclusion, the purified RPLCs, RILCs and RALCs are similar to those of their counterparts during rat pubertal development.

scholarly journals Development and Function of the Adult Generation of Leydig Cells in Mice with Sertoli Cell-Selective or Total Ablation of the Androgen Receptor

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4117-4126 ◽  
Author(s):  
Karel De Gendt ◽  
Nina Atanassova ◽  
Karen A. L. Tan ◽  
Luiz Renato de França ◽  
Gleydes Gambogi Parreira ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Growth Factor ◽  
Sertoli Cell ◽  
Leydig Cells ◽  
Platelet Derived Growth Factor ◽  
Testosterone Levels ◽  
Androgen Action ◽  
Serum Lh ◽  
D 12 ◽  
And Function

Abstract It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.

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