Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice

Shaojuan Lai, Brittany C. Collins, Brett A. Colson, Georgios Kararigas, Dawn A. Lowe

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23 Scopus citations

Abstract

Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone’s effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C2C12, pRLC was increased by 17β- estradiol (E2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mice (Sham). The reduced pRLC in OVX muscle was reversed by in vivo E2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E2 treatment, demonstrating physiological consequence. Western blot of those muscles revealed that low PTP corresponded with low pRLC and higher PTP with greater pRLC. We aimed to elucidate signaling pathways affecting E2-mediated pRLC using a kinase inhibitor library and C2C12 cells as well as a specific myosin light chain kinase inhibitor in muscles. PI3K/Akt, MAPK, and CamKII were identified as candidate kinases sensitive to E2 in terms of phosphorylating RLC. Applying siRNA strategy in C2C12 cells, pRLC triggered by E2 was found to be mediated by estrogen receptor- β and the G protein-coupled estrogen receptor. Together, these results provide evidence that E2modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females.

Original languageEnglish (US)
Pages (from-to)E724-E733
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume310
Issue number9
DOIs
StatePublished - May 1 2016

Bibliographical note

Funding Information:
Our research has been supported by National Institutes of Health Grants R01-AG-031743 (D. A. Lowe), K99-HL-122,397 (B. A. Colson), K02-AG- 036827 (D. A. Lowe), and T32-AR-07612 (B. C. Collins), a grant from the Office of the Vice President for Research, University of Minnesota (D. A. Lowe), and Project 31200801, supported by NSFC (S. Lai).

Publisher Copyright:
© 2016 the American Physiological Society.

Keywords

  • Estrogen
  • Estrogen receptor
  • Kinase
  • Post tetanic potentiation
  • RLC

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