A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health

Endocrinology. 2010 Sep;151(9):4289-300. doi: 10.1210/en.2010-0134. Epub 2010 Jun 23.


Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 +/- 0.42 g (VEH) versus 23.43 +/- 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 +/- 0.26 g (VEH) versus 19.78 +/- 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 +/- 0.48 g (VEH) versus 3.53 +/- 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 +/- 0.53 g (VEH) versus 4.57 +/- 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy.

MeSH terms

  • Activin Receptors, Type II / genetics
  • Activin Receptors, Type II / pharmacology*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Analysis of Variance
  • Androgen Antagonists / pharmacology*
  • Animals
  • Body Composition / drug effects*
  • Body Weight / drug effects
  • Bone Density / drug effects*
  • Cell Line
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin G / genetics
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / blood
  • Obesity / prevention & control
  • Orchiectomy
  • Random Allocation
  • Recombinant Fusion Proteins / pharmacology
  • Solubility


  • Androgen Antagonists
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Leptin
  • Recombinant Fusion Proteins
  • Activin Receptors, Type II
  • activin receptor type II-B