Estrogen replacement prevents ovariectomy‐induced muscle degradation via lowering local IGF‐1 production

Abstract

The prevalence of sarcopenia in women increases following menopause. Although muscle mass and circulating estrogens are positively correlated, the underlying mechanisms by which estrogen deficiency causes muscle atrophy is poorly understood. The present study examined the role of systemic and local IGF‐I in muscle maintenance of estrogen deficient rats. Eighteen 10‐month old female SD rats (n=6/group) were divided into either a sham operated group (sham) or two ovariectomized (ovx) groups receiving 17β‐estradiol (ovx+E2) or solvent vehicle (sham and ovx). All animals were pair‐fed for five months. Ovarian hormone deficiency did not cause atrophy in gastrocnemius (GAS) and soleus (SOL) muscle; however when muscle weight was normalized to body weight, the mean GAS value of ovx group was significantly lower than those of sham and E2 groups. Similarly, ovx mean SOL value tended (P<0.094) to be lower compared with other two groups. E2 treatment was able to prevent the ovx‐induced decreases in SOL, and GAS normalized values by 50% and 100%, respectively. Ovx significantly (P<0.05) increased systemic IGF‐I by 38% while local IGF‐I mRNA expressions were significantly decreased in both GAS (29%) and SOL (43%) samples of ovx rats. E2 administration prevented these decreases in IGF‐I levels. Our findings suggest that ovx‐induced elevation of systemic IGF‐I may down‐regulate its local mRNA expressions which in part can explain the loss of muscle mass in ovarian hormone deficiency.Grant Funding Source: Internal Funding