scholarly journals The Leydig Cell MEK/ERK Pathway Is Critical for Maintaining a Functional Population of Adult Leydig Cells and for Fertility

2011 ◽  
Vol 25 (7) ◽  
pp. 1211-1222 ◽  
Author(s):  
Soichi Yamashita ◽  
Ping Tai ◽  
Jean Charron ◽  
CheMyong Ko ◽  
Mario Ascoli
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Erk Pathway ◽  
Adult Leydig Cells

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 Interleukin-1alpha stimulates steroidogenic acute regulatory protein expression via p38 MAP kinase in immature rat Leydig cells

2003 ◽  
Vol 30 (1) ◽  
pp. 59-67 ◽  
Author(s):  
K Svechnikov ◽  
DM Stocco ◽  
O Soder
Keyword(s):  
Protein Expression ◽  
Map Kinase ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Regulatory Protein ◽  
P38 Map Kinase ◽  
Dependent Manner ◽  
Star Protein ◽  
Adult Leydig Cells ◽  
Steroidogenic Acute Regulatory

We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in interleukin-1alpha (IL-1alpha)-induced steroidogenesis in immature (40-day-old) and adult Leydig cells in vitro. Further, IL-1alpha-mediated signaling pathway(s) controlling StAR expression in immature Leydig cells were also studied. IL-1alpha stimulated both androgen production and StAR protein expression in a dose- and time-dependent manner in immature but not adult Leydig cells. These effects of IL-1alpha were prevented by pretreatment of the cells with the specific inhibitors of the p38 MAP kinase, SB203580 and PD169316, suggesting that this kinase is an important part of IL-1alpha signaling in the immature Leydig cell. The present results suggest that IL-1alpha, which is constitutively produced by the rat testis from postnatal day 25, is an important paracrine regulator of postnatal Leydig cell maturation. Regulation of StAR protein expression is one of the possible mechanisms by which IL-1alpha contributes to the differentiation of immature Leydig cells into adult cells.

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 Effects of Osteocalcin on Synthesis of Testosterone and INSL3 during Adult Leydig Cell Differentiation

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Gulfidan Coskun ◽  
Leman Sencar ◽  
Abdullah Tuli ◽  
Dilek Saker ◽  
Mustafa Muhlis Alparslan ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Postnatal Development ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Development Process ◽  
Gnrh Antagonist ◽  
Serum Testosterone ◽  
Male Rats ◽  
Significant Difference ◽  
Adult Leydig Cells

Proliferation and differentiation of adult Leydig cells are mainly completed in puberty. In many studies, apart from normal postnatal development process, it is widely indicated that, through administrating EDS, Leydig cell population is eliminated and regenerated. It is believed that osteocalcin released from osteoblasts, which is responsible for modulating bone metabolism, induces testosterone production in Leydig cells, independent of the HPG axis. In addition, INSL3 produced by Leydig cells, such as testosterone, plays a critical role in bone metabolism and is known to reflect the development process and functional capacities of Leydig cells. This study is aimed at investigating OC-mediated testosterone regulation and INSL3 synthesis during differentiation of adult Leydig cells that are independent of LH. For this purpose, male rats were divided into 2 groups: prepubertal normal rats and adult EDS-injected rats. Each group was divided into 4 subgroups in which GnRH antagonist or OC was applied. After adult Leydig cells completed their development, testicular tissue samples obtained from the sacrificed rats were examined by light-electron microscopic, immunohistochemical, and biochemical methods. Slight upregulation in 3βHSD, INSL3, and GPRC6A expressions along with the increase in serum testosterone levels was observed in groups treated with osteocalcin against GnRH antagonist. In addition, biochemical and microscopic findings in osteocalcin treated groups were similar to those in control groups. While there was no significant difference in the number of Leydig cells reported, the presence of a significant upregulation in INSL3 and GPRC6A expressions and the increase in serum testosterone and ucOC levels were observed. After evaluation of findings altogether, it is put forward that, for the first time in this study, although osteocalcin treatment made no significant difference in the number of Leydig cells, it increased the level of testosterone through improving the function of existing adult Leydig cells during normal postnatal development process and post-EDS regeneration. This positive correlation between osteocalcin-testosterone and osteocalcin-INSL3 is concluded to be independent of LH at in vivo conditions.

Trimethyltin (TMT) Reduces Testosterone Production in Adult Leydig Cells in Rats

2019 ◽  
Vol 38 (6) ◽  
pp. 493-500 ◽  
Author(s):  
Derong Ma ◽  
Nengqin Luo ◽  
Guoqiang Xue
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Follicle Stimulating Hormone ◽  
Regulatory Protein ◽  
Cell Number ◽  
Severe Toxicity ◽  
Testosterone Production ◽  
Gene And Protein Expression ◽  
Adult Leydig Cells ◽  
Stimulating Hormone

Trimethyltin (TMT) is widely used as a plastic heat stabilizer and can cause severe toxicity. Here, the effects of TMT on testosterone production by adult Leydig cells and the related mechanisms of action were investigated. Eighteen adult male Sprague Dawley rats (56 days old) were randomly divided into 3 groups and given intraperitoneal injection of TMT for 21 consecutive days at the doses of 0 (vehicle control), 5, or 10 mg/kg/d. After treatment, trunk blood was collected for hormonal analysis. In addition, related gene and protein expression in testes was detected. At 10 mg/kg, TMT significantly reduced serum testosterone levels but increased serum luteinizing and follicle-stimulating hormone levels. The messenger RNA and protein levels of luteinizing hormone/chorionic gonadotropin receptor, steroidogenic acute regulatory protein, cytochrome P450 17-hydroxylase/17,20-lyase, follicle-stimulating hormone receptor, and SRY box 9 were significantly lower in the TMT-treated testes than in controls. Immunohistochemical study showed that TMT decreased adult Leydig cell number. In conclusion, these findings indicate that TMT reduced adult Leydig cell testosterone production in vivo by directly downregulating the expression of steroidogenic enzymes and decreasing adult Leydig cell number in the testis.

Androgen receptor signalling in testicular Leydig cells is essential for Leydig cell maturation and survival

2014 ◽  
Author(s):  
Laura O'Hara ◽  
Kerry McInnes ◽  
Ioannis Simitsidellis ◽  
Steph Morgan ◽  
Laura Milne ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Maturation ◽  
Receptor Signalling

A review of drug-induced Leydig cell hyperplasia and neoplasia in the rat and some comparisons with man

1995 ◽  
Vol 14 (7) ◽  
pp. 562-572 ◽  
Author(s):  
DE Prentice ◽  
AW Meikle
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Safety Assessment ◽  
Hormonal Status ◽  
Control Mechanisms ◽  
Hormone Production ◽  
Drug Induced ◽  
Cell Hyperplasia ◽  
Etiological Factors ◽  
Func Tion

This paper describes control of normal Leydig cell func tion and testosterone production. The macroscopic and histopathological appearances of spontaneous Leydig cell hyperplasias and tumors (LCT) in the rat are reviewed together with their incidence and hormonal status. Drugs which induce LCTs in chronic studies are discussed and include busereline, carbamazepine, cimetidine, finas teride, flutamide, gemfibrozil, histrelin, hydralazine, indomethacin, isradipine, lactitol, leuprolide, metronida zole, mesulergine, nafarelin, norprolac and vidarabine. The known mechanisms of LCT induction in the rat are reviewed together with other possible etiological factors. The incidence, clinical picture and etiological factors of LCTs in man are also surveyed. Hormone production in Leydig cells and LCTs in rats and man are compared. Differences between the two species are considered, par ticularly with regard to Leydig cell control mechanisms. The paper concludes that drug-induced LCTs in rats are most probably not predictive for man and their occurrence has little relevance in human safety assessment.

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