Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats

Wenqing Gao, Peter J. Reiser, Christopher C. Coss, Mitch A. Phelps, Jeffrey D. Kearbey, Duane Miller, James T. Dalton

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy) -2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights moire than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

Original languageEnglish (US)
Pages (from-to)4887-4897
Number of pages11
JournalEndocrinology
Volume146
Issue number11
DOIs
StatePublished - Nov 1 2005

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Dihydrotestosterone
Androgen Receptors
Muscle Strength
Body Composition
Bone and Bones
Anabolic Agents
Prostate
Skeletal Muscle
Castration
Muscles
Seminal Vesicles
Anal Canal
Bone Density
Androgens
Weights and Measures
Therapeutics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. / Gao, Wenqing; Reiser, Peter J.; Coss, Christopher C.; Phelps, Mitch A.; Kearbey, Jeffrey D.; Miller, Duane; Dalton, James T.

In: Endocrinology, Vol. 146, No. 11, 01.11.2005, p. 4887-4897.

Research output: Contribution to journalArticle

Gao, Wenqing ; Reiser, Peter J. ; Coss, Christopher C. ; Phelps, Mitch A. ; Kearbey, Jeffrey D. ; Miller, Duane ; Dalton, James T. / Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. In: Endocrinology. 2005 ; Vol. 146, No. 11. pp. 4887-4897.
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