Estradiol deficiency impairs satellite cell function and causes muscle weakness via an estrogen receptor alpha mediated mechanism

Abstract

Overall, my dissertation work has shown that estradiol is a critical extrinsic factor in females that regulates muscle stem cell (i.e. satellite cell) and skeletal muscle function (Chapters 3 and 4) and estrogen receptor alpha (ER) is the main receptor estradiol utilizes for these functions (Chapters 3 and 4). I identified that the loss of ovarian hormones resulted in impaired satellite cell functions such as maintenance and self-renewal, while estradiol treatment rescued the detrimental effects on satellite cell maintenance and self-renewal (Chapter 3). Further experiments utilized a transgenic mouse that specifically ablated ER in satellite cells, the results of which indicated that ER is necessary for proper satellite cell function (Chapter 3). In agreement with my work on satellite cells, I identified that ER is necessary for overall skeletal muscle function (Chapter 4). I utilized a transgenic mouse model that deleted ER specifically from skeletal muscle fibers which resulted in impairments in strength, power, and fatiguability of skeletal muscle (Chapter 4). The work of my dissertation highlights a novel mechanism for estradiol and ER in skeletal muscle.