This Article Full Text Full Text (PDF) All Versions of this Article: 146/11/4887    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gao, W. Articles by Dalton, J. T. Search for Related Content PubMed PubMed Citation Articles by Gao, W. Articles by Dalton, J. T.

Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats

Division of Pharmaceutics (W.G., C.C.C., M.A.P., J.D.K., J.T.D.), College of Pharmacy and Department of Oral Biology (P.J.R.), College of Dentistry, The Ohio State University, Columbus, Ohio 43210; and Department of Pharmaceutical Sciences (D.D.M.), College of Pharmacy, University of Tennessee, Memphis, Tennessee 38163

Address all correspondence and requests for reprints to: James T. Dalton, Ph.D., The Ohio State University, 500 West 12th Avenue, L. M. Parks Hall, Room 242, Columbus, Ohio 43210. E-mail: dalton.1{at}osu.edu.

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.

This article has been cited by other articles:

				S. T. Page, J. K. Amory, and W. J. Bremner Advances in Male Contraception Endocr. Rev., June 1, 2008; 29(4): 465 - 493. [Abstract] [Full Text] [PDF]

				T. Kuuranne, A. Leinonen, W. Schanzer, M. Kamber, R. Kostiainen, and M. Thevis Aryl-Propionamide-Derived Selective Androgen Receptor Modulators: Liquid Chromatography-Tandem Mass Spectrometry Characterization of the in Vitro Synthesized Metabolites for Doping Control Purposes Drug Metab. Dispos., March 1, 2008; 36(3): 571 - 581. [Abstract] [Full Text] [PDF]

				W. Gao and J. T. Dalton Ockham's Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5{alpha}-Reductase? Mol. Interv., February 1, 2007; 7(1): 10 - 13. [Abstract] [Full Text] [PDF]

				J. N. Miner, W. Chang, M. S. Chapman, P. D. Finn, M. H. Hong, F. J. Lopez, K. B. Marschke, J. Rosen, W. Schrader, R. Turner, et al. An Orally Active Selective Androgen Receptor Modulator Is Efficacious on Bone, Muscle, and Sex Function with Reduced Impact on Prostate Endocrinology, January 1, 2007; 148(1): 363 - 373. [Abstract] [Full Text] [PDF]

				A M Solomon and P M G Bouloux Modifying muscle mass - the endocrine perspective. J. Endocrinol., November 1, 2006; 191(2): 349 - 360. [Abstract] [Full Text] [PDF]

				J. Yang, C. E. Bohl, V. A. Nair, S. M. Mustafa, S. S. Hong, D. D. Miller, and J. T. Dalton Preclinical Pharmacology of a Nonsteroidal Ligand for Androgen Receptor-Mediated Imaging of Prostate Cancer J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 402 - 408. [Abstract] [Full Text] [PDF]

				W. Gao, J. S. Johnston, D. D. Miller, and J. T. Dalton INTERSPECIES DIFFERENCES IN PHARMACOKINETICS AND METABOLISM OF S-3-(4-ACETYLAMINO-PHENOXY)-2-HYDROXY-2-METHYL-N-(4-NITRO-3-TRIFLUOROMETHYLPHENYL)-PROPIONAMIDE: THE ROLE OF N-ACETYLTRANSFERASE Drug Metab. Dispos., February 1, 2006; 34(2): 254 - 260. [Abstract] [Full Text] [PDF]