Androgen uptake and binding in rat epididymal nuclei, in vivo

Tindall, Donald J.; French, Frank S.; Nayfeh, Shihadeh N.

doi:10.1016/0006-291x(72)90493-7

Cited by 76 publications

(18 citation statements)

References 6 publications

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“…Several key findings led to this conclusion. The first is that the active androgen present in epididymal cell nuclei after injection of radio labelled testosterone is DHT (Tindall, 1972). The second is that epididymal tissue can synthesize Sa-reduced metabolites from testosterone in vitro (Gloyna and Wilson, 1969;Robaire et al, 1977).…”

Section: The Active Androgen In the Epididymismentioning

confidence: 98%

The Coming of Age of the Epididymis

Robaire¹,

Syntin²,

Jervis³

2000

Testis, Epididymis and Technologies in the Year 2000

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Section: The Active Androgen In the Epididymismentioning

confidence: 98%

The Coming of Age of the Epididymis

Robaire¹,

Syntin²,

Jervis³

2000

Testis, Epididymis and Technologies in the Year 2000

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“…More specifically, several studies have clearly shown that the primary androgen acting in this tissue is dihydrotestosterone (DHT) (Gloyna & Wilson 1969, Tindall et al 1972, Orgebin-Crist et al 1976, Turner et al 1984. 5a-Reductase (EC 1.3.1.22) is the enzyme that catalyzes the conversion of testosterone to DHT.…”

Section: Introductionmentioning

confidence: 99%

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Henderson¹,

Cooke²,

Robaire³

2006

Journal of Endocrinology

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Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the site of sperm maturation. Previously, we showed that the treatment of male rats with PNU157706, an inhibitor that acts on both isoforms of 5a-reductase to prevent DHT formation, has effects on the expression of genes implicated in processes that create the optimal luminal microenvironment required for sperm maturation, and on sperm maturation itself. However, signaling pathways involved in regulating or mediating DHT actions in the epididymis remain largely unknown. The goals of this study were to determine the expression profiles of potential signaling systems in the epididymis and assess their DHTdependence using two different dual 5a-reductase inhibitors. Rats were untreated or gavaged with vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and epididymal gene expression was analyzed. Gene array analysis revealed analogous effects of FK143 on overall epididymal gene expression when compared with previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the 5a-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF, and VEGF families revealed novel region-specific expression profiles in the epididymis that were differentially affected by 5a-reductase inhibition; the two inhibitors had parallel effects. Specifically, in proximal regions, 5a-reductase 1, androgen receptor, and TGF-b1 expression increased after treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF-10 decreased. These results provide insight into epididymal signaling mechanisms and indicate potential candidates acting either upstream or downstream of DHT to regulate and/or mediate its actions in the epididymis.

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“…Androgens, however, are recognized as the primary hormonal regulators of epididymal structure and functions (Blaquier et al 1972, Orgebin-Crist & Tichenor 1973. Furthermore, several in vivo and in vitro studies have confirmed that it is not testosterone, but rather dihydrotestosterone (DHT), that is the main androgen acting in this tissue (Gloyna & Wilson 1969, Tindall et al 1972, Orgebin-Crist et al 1976, Turner et al 1984. 5 -Reductase (EC 1·3·1·22) is thus a key enzyme in the epididymis because of its role in locally converting testosterone to DHT.…”

Section: Introductionmentioning

confidence: 99%

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis

Henderson¹,

Cooke²,

Robaire³

2004

Journal of Endocrinology

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The epididymis is the site of sperm maturation and storage. 5 -Reductases (types 1 and 2) are key enzymes in this tissue because they convert testosterone to dihydrotestosterone (DHT), the main androgen regulating epididymal functions. Examining the consequences of inhibiting DHT formation is likely to provide important information regarding the regulation of epididymal functions, yet few inhibitor studies have focused on this tissue. To understand better DHT-mediated regulation of epididymal gene expression, we employed a dual 5 -reductase inhibitor and cDNA microarrays to examine the effects of 5 -reductase inhibition on gene expression in the initial segment, caput, corpus, and cauda epididymidis. Inhibition of epididymal 5 -reductase activity by PNU157706 was confirmed by in vitro enzyme assays. Rats were treated with 0, 0·1, 1·0 or 10 mg/kg per day PNU157706 for 28 days. The weights of DHT-dependent tissues, including the epididymis, were decreased following treatment. The effect of treatment on gene expression was dose-dependent and highly segment-specific. The initial segment responded uniquely in that a similar number of genes increased and decreased in expression compared with the other segments where the majority of affected genes decreased in expression. Some of the more dramatically affected genes were involved in signal transduction as well as fatty acid and lipid metabolism, regulation of ion and fluid transport, luminal acidification, oxidative defense and protein processing and degradation. These are essential processes contributing to the formation of an optimal luminal microenvironment required for proper sperm maturation. These results provide a novel insight into the DHT-dependent mechanisms that control epididymal functions.

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Androgen uptake and binding in rat epididymal nuclei, in vivo

Cited by 76 publications

References 6 publications

The Coming of Age of the Epididymis

The Coming of Age of the Epididymis

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis

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