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As life expectancy continues to rise, the number of people over age 65 in the U.S. is increasing. An aging population brings with it impacts on the national health system and associated economic expenditures. As individuals age, the skeletomuscular system suffers reduced function due to disease or conditions such as sarcopenia. Sarcopenia is characterized by muscular atrophy resulting from reduced muscle innervation. Exercise has been linked to prevention of sarcopenia, a suspected result of increased production of glial cell line-derived neurotrophic factor (GDNF). GDNF promotes neuronal survival, regeneration, and the formation of neuromuscular junctions. Therefore, treatments like exercise that increase GDNF expression by skeletal muscle cells could be used as possible preventative measures for sarcopenia. It is well known that skeletal muscle structure differs between the sexes, and prior studies have shown that males have a higher incidence of sarcopenia compared to females. This raises the possibility that differences in sex hormones could be responsible for reduced muscular atrophy observed in females. Estrogen is one such hormone that is important for sexual development in females (although it is produced in low levels by male gonads). It is currently unclear if estrogen is responsible for neuroprotection in female skeletal muscle. The aim of this study was to observe the effects of E2 (estradiol) estrogen treatments on levels of GDNF production in C2C12 skeletal muscle cells. To test this, we treated murine myotubes with estradiol in vitro and quantified GDNF protein levels using an enzyme-linked immunosorbent assay (ELISA). The results of this study suggest that estradiol treatments of 5 nM and 100 nM lead to decreased GDNF production 4 hours after treatment. When compared to the control, the 5 nM estradiol treated cells produced an increase in GDNF at 48 hours. Our data indicate that chronic estradiol exposure could increase GDNF production in skeletal muscle in vitro, highlighting a potential mechanism by which estrogen could lead to the reduced incidence of sarcopenia in females.
Welter, Hope, "The Effect of Estrogen on GDNF Production of Skeletal Muscle In Vitro" (2022). Honors Theses. 3575.
Honors Thesis-Open Access