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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/E507    most recent 00130.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Borst, S. E. Articles by Wronski, T. J. Search for Related Content PubMed PubMed Citation Articles by Borst, S. E. Articles by Wronski, T. J.

Anabolic effects of testosterone are preserved during inhibition of 5-reductase

¹Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center; Departments of ²Applied Physiology and Kinesiology, ³Aging and Geriatric Research, ⁴Physical Therapy, and ⁵Physiological Sciences, University of Florida, Gainesville, Florida

Submitted 26 February 2007 ; accepted in final form 30 April 2007

At replacement doses, testosterone produces only modest increases in muscle strength and bone mineral density in older hypogonadal men. Although higher doses of testosterone are more anabolic, there is concern over increased adverse effects, notably prostate enlargement. We tested a novel strategy for obtaining robust anabolic effects without prostate enlargement. Orchiectomized (ORX) male rats were treated for 56 days with 1.0 mg testosterone/day, with and without 0.75 mg/day of the 5-reductase inhibitor MK-434. Testosterone administration elevated the prostate dihydrotestosterone concentration and caused prostate enlargement. Both effects were inhibited by MK-434. ORX produced a catabolic state manifested in reduced food intake, blunted weight gain, reduced hemoglobin concentration, decreased kidney mass, and increased bone resorption, and in the proximal tibia there was both decreased cancellous bone volume and a decreased number of trabeculae. In soleus and extensor digitorum longus muscles, ORX reduced both the percentage of type I muscle fibers and the cross-sectional area of type 1 and 2 fibers. Testosterone administration caused a number of anabolic effects, including increases in food intake, hemoglobin concentration, and grip strength, and reversed the catabolic effects of ORX on bone. Testosterone administration also partially reversed ORX-induced changes in muscle fibers. In contrast to the prostate effects of testosterone, the effects on muscle, bone, and hemoglobin concentration were not blocked by MK-434. Our study demonstrates that the effects of testosterone on muscle and bone can be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.

dihydrotestosterone; prostate; body composition; bone resorption

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