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ORIGINAL RESEARCH ARTICLE

Estrogen Effects on Skeletal Muscle Insulin-Like Growth Factor–1 and Myostatin in Ovariectomized Rats

Wan-Jung A. Tsai^*, Kathleen M. McCormick, Daniel A. Brazeau^* and Gayle A. Brazeau^*,1

^* Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Amherst, New York 14260; and Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York 14214

To whom requests for reprints should be addressed at ¹ Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, 517 Hochstetter Hall, North Campus, University at Buffalo, Amherst, New York 14260. E-mail: gbrazeau{at}acsu.buffalo.edu

Previous work showed that estrogen replacement attenuates muscle growth in immature rats. The present study examined muscle insulin-like growth factor–1 (IGF-1) and myostatin expression to determine whether these growth regulators might be involved in mediating estrogen’s effects on muscle growth. IGF-1 and myostatin message and protein expression in selected skeletal muscles from 7-week-old sham-ovariectomized (SHAM) and ovariectomized rats that received continuous estrogen (OVX/E2) or solvent vehicle (OVX/CO) from an implant for 1 week or 5 weeks was measured. In the 1-week study, ovariectomy increased IGF-1 mRNA expression in fast extensor digitorum longus and gastrocnemius muscles; the increase was reversed by estrogen replacement. A similar trend was observed in the slow soleus muscle, although the change was not statistically significant. In contrast to mRNA, muscle IGF-1 protein expression was not different between SHAM and OVX/ CO animals in the 1-week study. One week of estrogen replacement significantly decreased IGF-1 protein level in all muscles examined. Myostatin mRNA expression was not different among the 1-week treatment groups. One week of estrogen replacement significantly increased myostatin protein in the slow soleus muscle but not the fast extensor digitorum longus and gastrocnemius muscles. There was no treatment effect on IGF-1 and myostatin expression in the 5-week study; this finding suggested a transient estrogen effect or upregulation of a compensatory mechanism to counteract the estrogen effect observed at the earlier time point. This investigation is the first to explore ovariectomy and estrogen effects on skeletal muscle IGF-1 and myostatin expression. Results suggest that reduced levels of muscle IGF-1 protein may mediate estrogen’s effect on growth in immature, ovariectomized rats. Increased levels of muscle myostatin protein may also have a role in mediating estrogen’s effects on growth in slow but not fast skeletal muscle.

Key Words: estrogen • myostatin • IGF-1 • ovariectomy • skeletal muscle • growth