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Endocrine

, Volume 32, Issue 1, pp 41–51 | Cite as

A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats

  • George F. AllanEmail author
  • Pamela Tannenbaum
  • Tifanie Sbriscia
  • Olivia Linton
  • Muh-Tsann Lai
  • Donna Haynes-Johnson
  • Sheela Bhattacharjee
  • Xuqing Zhang
  • Zhihua Sui
  • Scott G. Lundeen
Original Paper

Abstract

Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-28330835 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle, stimulating maximal growth at a dose of 10 mg/kg. At the same time, JNJ-28330835 reduced prostate weight in intact rats by a mean of 30% at 10 mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging (MRI) to monitor body composition, it prevented half of the loss of lean body mass associated with orchidectomy, and restored about 30% of lost lean mass to aged orchidectomized rats. It had agonist effects on markers of both osteoclast and osteoblast activity, suggesting that it reduces bone turnover. In a model of sexual behavior, JNJ-28330835 enhanced the preference of ovariectomized female rats for sexually intact male rats over nonsexual orchidectomized males. JNJ-28330835 is a prostate-sparing SARM with the potential for clinically beneficial effects in muscle-wasting diseases and sexual function disorders.

Keywords

Selective androgen receptor modulator Prostate Lean body mass Sexual function 

Notes

Acknowledgments

We thank Z. Hu and R. Russell for the large-scale synthesis of JNJ-28330835.

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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • George F. Allan
    • 1
    Email author
  • Pamela Tannenbaum
    • 1
  • Tifanie Sbriscia
    • 1
  • Olivia Linton
    • 1
  • Muh-Tsann Lai
    • 1
  • Donna Haynes-Johnson
    • 1
  • Sheela Bhattacharjee
    • 1
  • Xuqing Zhang
    • 1
  • Zhihua Sui
    • 1
  • Scott G. Lundeen
    • 1
  1. 1.Reproductive TherapeuticsJohnson & Johnson Pharmaceutical Research and Development, L.L.C.RaritanUSA

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