Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis
in Journal of EndocrinologySearch for other papers by NA Henderson in
Current site
Google Scholar
PubMed
Search for other papers by GM Cooke in
Current site
Google Scholar
PubMed
Search for other papers by B Robaire in
Current site
Google Scholar
PubMed
The epididymis is the site of sperm maturation and storage. 5alpha-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 5alpha-reductase inhibitor and cDNA microarrays to examine the effects of 5alpha-reductase inhibition on gene expression in the initial segment, caput, corpus, and cauda epididymidis. Inhibition of epididymal 5alpha-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.
Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.
The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.
More information is on the Reasons to publish page.
| Sept 2018 onwards | Past Year | Past 30 Days | |
|---|---|---|---|
| Full Text Views | 146 | 64 | 3 |
| PDF Downloads | 124 | 36 | 4 |
Online ISSN: 1479-6805
Print ISSN: 0022-0795
Strengthening biomedical communities
to advance science and health
CONTACT US
Bioscientifica Ltd | Starling House | 1600 Bristol Parkway North | Bristol BS34 8YU | UK
Bioscientifica Ltd | Registered in England no 3190519