A Soluble Activin Receptor Type IIB Prevents the Effects of Androgen Deprivation on Body Composition and Bone Health

被引：66

作者：

Koncarevic, Alan ^{[1
]}

Cornwall-Brady, Milton ^{[1
]}

Pullen, Abigail ^{[1
]}

Davies, Monique ^{[1
]}

Sako, Dianne ^{[1
]}

Liu, June ^{[1
]}

Kumar, Ravindra ^{[1
]}

Tomkinson, Kathleen ^{[1
]}

Baker, Theresa ^{[1
]}

Umiker, Ben ^{[1
]}

Monnell, Travis ^{[1
]}

Grinberg, Asya V. ^{[1
]}

Liharska, Katia ^{[1
]}

Underwood, Kathryn W. ^{[1
]}

Ucran, Jeffrey A. ^{[1
]}

Howard, Elizabeth ^{[1
]}

Barberio, Joseph ^{[1
]}

Spaits, Matthew ^{[1
]}

Pearsall, Scott ^{[1
]}

Seehra, Jasbir ^{[1
]}

Lachey, Jennifer ^{[1
]}

机构：

[1] Acceleron Pharma Inc, Cambridge, MA 02139 USA

来源：

ENDOCRINOLOGY | 2010年 / 151卷 / 09期

关键词：

SKELETAL-MUSCLE; IMPROVES FUNCTION; ADIPOSE-TISSUE; MYOSTATIN; TESTOSTERONE; GENE; MASS; EXPRESSION; MICE; OSTEOPOROSIS;

D O I：

10.1210/en.2010-0134

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 dualx-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. (Endocrinology 151: 4289-4300, 2010)

引用

页码：4289 / 4300

页数：12

共 41 条

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