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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/F307    most recent 00135.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Xu, Q. Articles by Maric, C. PubMed PubMed Citation Articles by Xu, Q. Articles by Maric, C.

Dose-dependent effects of dihydrotestosterone in the streptozotocin-induced diabetic rat kidney

¹Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia; and ²Department of Physiology and Biophysics and ³Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, Mississippi

Submitted 8 March 2009 ; accepted in final form 2 June 2009

We recently reported that castration exacerbates albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis associated with diabetic renal disease. The aim of the present study was to examine whether these effects of castration can be attenuated with dihydrotestosterone (DHT) supplementation. The study was performed in castrated male Sprague-Dawley, streptozotocin-induced diabetic rats treated with 0 mg/day DHT (DHT₀), 0.75 mg/day DHT (DHT_0.75), or 2.0 mg/day DHT (DHT_2.0) for 14 wk. Treatment with 0.75 mg/day DHT attenuated castration-associated increases in urine albumin excretion (DHT₀, 81.2 ± 18.1; DHT_0.75, 26.57 ± 5.8 mg/day; P < 0.05), glomerulosclerosis (DHT₀, 1.1 ± 0.79; DHT_0.75, 0.43 ± 0.043 arbitrary units; P < 0.001), tubulointerstitial fibrosis (DHT₀, 1.3 ± 0.12; DHT_0.75, 1.1 ± 0.096 AU; P < 0.05), collagen type IV [DHT₀, 3.2 ± 0.11; DHT_0.75, 2.1 ± 0.070 relative optical density (ROD); P < 0.01], transforming growth factor-β (DHT₀, 3.2 ± 0.16; DHT_0.75, 2.1 ± 0.060 ROD; P < 0.01), IL-6 (DHT₀, 0.37 ± 0.011; DHT_0.75, 0.27 ± 0.014 ROD; P < 0.05), and protein expression and reduced CD68-positive cell abundance (DHT₀, 17 ± 0.86; DHT_0.75, 4.4 ± 0.55 cells/mm²; P < 0.001). In contrast, treatment with 2.0 mg/day DHT exacerbated all these parameters. These data suggest that the detrimental effects of castration in the diabetic kidney can be attenuated with low doses of DHT, whereas high doses augment the adverse effects of castration, and these effects appear to be influenced by estradiol. We conclude that the effects of DHT are dose dependent but caution should be taken when DHT supplementation is considered in the treatment of diabetic renal disease.

diabetes; glomerulosclerosis; tubulointerstitial fibrosis; sex hormones