Effects of Androgen on Androgen Receptor Expression in Rat Testicular and Epididymal Cells: A Quantitative Immunohistochemical Study1

Zhu, Lian; Hardy, Matthew P.; Inigo, Ivan; Huhtaniemi, Ilpo; Bardin, C. Wayne; Moo-Young, Alfred J.

doi:10.1095/biolreprod63.2.368

Cited by 119 publications

(86 citation statements)

References 39 publications

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“…AR proteins were localized in both the epithelial and stromal cells of all of the male reproductive tissues examined in the present study, which is essentially in accordance with results obtained previously by immunohistochemistry and steroid autoradiography (Schleicher et al, 1985;Sar et al, 1990;Prins and Birch, 1993;Pelletier et al, 2000;Zhu et al, 2000;Zhou et al, 2002). On the other hand, ER␣ and ER␤ were expressed in cell-type-and species-specific manners.…”

Section: Discussionsupporting

confidence: 93%

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

Yamashita

2004

Anat. Rec.

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Using immunohistochemical methods, we studied the cell-type-and species-specific expressions of estrogen receptor (ER) isoforms (ER␣ and ER␤) and androgen receptors (ARs) in the male reproductive tract and accessory sex glands of mature mice and rats. ER␣ and ER␤ showed cell-type-and species-specific distributions, respectively. In contrast, AR was localized in the epithelial and stroma cells of all tissues examined in this study, in both species. In mice, the epithelial cells of the ductuli efferentes showed a strong ER␣-immunoreaction, and those of the caput epididymis, coagulating glands, and prostate also exhibited a positive reaction. Stroma cells, except in the ductuli efferentes, showed a positive ER␣-immunostaining. In rats, ER␣ was detected in very few cell types: the epithelial cells of the ductuli efferentes showed a strong reaction, and the stroma cells of the ampullary and urethral glands exhibited a weak reaction. ER␤ was localized in the epithelial cells of the prostate in mice, while the reaction was faint or negative in both the epithelial and stroma cells of other tissues. In rats, the ER␤-immunoreaction was strongest in the epithelial cells of the ventral prostate. The epithelial cells of the corpus and cauda epididymis, ductus deferens, and urethral glands, and the stroma cells of the urethral glands were also positively ER␤-immunostained. Almost the same AR distribution pattern was observed in both species. In particular, strong AR-immunostaining was present in the epithelial cells of the caput and corpus epididymis, seminal vesicle, and ventral prostate. These results indicate that species and tissues differences should be taken into careful consideration in assessing the physiological and pharmacological effects of sex steroids (particularly estrogens) on the reproductive tissues of male rodents.

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Section: Discussionsupporting

confidence: 93%

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

Yamashita

2004

Anat. Rec.

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“…Androgen receptors were identified by immunohistochemistry and immunocytochemistry in Leydig cells from young adult Syrian hamsters in agreement with previous reports in mice (Pelletier 2000, Zhou et al 2002, rats (Pelletier 2000, Zhu et al 2000, pigs (Christensen 1996) and humans (Van Roijen et al 1995, Figure 8 Immunolocalization of androgen receptors in Syrian hamster testes. Positive immunostaining for androgen receptor (AR) was found in Leydig cells (arrowhead), Sertoli cells (black arrow) and myoid cells (white arrow) in testes from young adult (90-day-old) Syrian hamsters kept under a long-day (LD) photoperiod (14 h light:10 h darkness) (A).…”

Section: Testosterone Induces Testicular Ptgs2supporting

confidence: 89%

Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig cells

Matzkin¹,

González-Calvar²,

Mayerhofer³

et al. 2009

Reproduction

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We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF 2a on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF 2a . In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF 2a production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF 2a in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF 2a inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

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“…The effects of testosterone are mediated through its receptor (AR), the levels of which are, in turn, regulated by androgen. 29 In Figure 4 Attenuated CoCl 2 -induced HIF-1a stabilization in 100-nmol l 21 testosterone-treated TM3 cells. Cells were incubated with testosterone at 37 uC for 48 h, and then HIF-1a stabilization was examined by a western blot analysis.…”

Section: Discussionmentioning

confidence: 98%

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

Hwang¹,

Liao²,

Lin³

et al. 2011

Asian J Androl

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Testosterone replacement therapy has benefits for aging men and those with hypogonadism. However, the effects of exogenous testosterone on Leydig cells are still unclear and need to be clarified. In this report, we demonstrate that testosterone supplementation can reduce oxidative damage in Leydig cells. The TM3 Leydig cell line was used as an in vitro cell model in this study. Cytoprotective effects were identified with 100-nmol l 21 testosterone treatment, but cytotoxic effects were found with o500-nmol l 21 testosterone supplementation. Significantly reduced reactive oxygen species (ROS) generation, lipid peroxide contents and hypoxia induction factor (HIF)-1a stabilization and activation were found with 100-nmol l 21 testosterone treatment. There was a 1.72-fold increase in ROS generation in the 500-nmol l 21 compared to the 100-nmol l 21 testosterone treatment. A 1.58-fold increase in steroidogenic acute regulatory protein (StAR) expression was found in 50-nmol l 21 testosterone-treated cells (P,0.01). Chemically induced hypoxia was attenuated by testosterone supplementation. Leydig cells treated with low-dose testosterone supplementation showed cytoprotection by decreasing ROS and lipid peroxides, increasing StAR expression and relieving hypoxia stress as demonstrated by HIF-1a stabilization. Increased oxidative damage was found with o500-nmol l 21 testosterone manipulation. The mechanism governing the differential dose effects of testosterone on Leydig cells needs further investigation in order to shed light on testosterone replacement therapy. INTRODUCTIONTestosterone plays an important role in normal growth and development of male sex organs. It is also known to be a key player in glucose homeostasis and lipid metabolism. 1 More recently, gonadotrophinreleasing hormones I and II were demonstrated to stimulate testosterone production in murine Leydig cells. 2 In the testes, Leydig cells synthesize and secrete testosterone in response to luteinizing hormone, which is counter-regulated by feedback influences of testosterone and its metabolites. Testosterone levels notably decline with aging; 3,4 however, a recent report showed no correlation between androgen receptor (AR) polymorphism and the serum concentrations of total and free testosterone in elderly men. 5 The mechanism by which aged Leydig cells lose their steroidogenic function remains unclear. It was proposed that decreases in testosterone levels with aging may reflect reactive oxygen species (ROS) elevation and further disruption of the ability of Leydig cells to produce testosterone. 6,7 Mitochondrial respiration, which typically consumes about 90% of the oxygen utilized by cells, is considered to be the major source of cellular ROS. 8 ROS cause tissue damage by a variety of mechanisms including DNA damage, lipid peroxidation, protein oxidation and carbonylation, depletion of cellular thiols and activation of proinflammatory cytokine release. Mitochondrial-derived ROS were implicated in a number of disease and disorders, including neurodegenerat...

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Effects of Androgen on Androgen Receptor Expression in Rat Testicular and Epididymal Cells: A Quantitative Immunohistochemical Study1

Cited by 119 publications

References 39 publications

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig cells

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

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