title: Time since menopause and skeletal muscle estrogen receptors, PGC-1α, and AMPK.
abstract: OBJECTIVE
  Short-term administration of estradiol (E2) improves insulin-stimulated glucose disposal rate in early postmenopausal (EPM) women compared with a reduction in late postmenopausal (LPM) women. The underlying mechanisms by which E2 action on glucose disposal rate reversed from beneficial early to harmful late in menopause is unknown, but might include adverse changes in estrogen receptors (ERs) or other biomarkers of cellular energy metabolism with age or duration of estrogen deficiency.
  
  
  METHODS
  We retrospectively analyzed skeletal muscle samples from 27 postmenopausal women who were 6 years or less past menopause (EPM; n = 13) or at least 10 years past menopause (LPM; n = 14). Fasted skeletal muscle (vastus lateralis) samples were collected after 1 week administration of transdermal E2 or placebo, in random cross-over design.
  
  
  RESULTS
  Compared with EPM, LPM had reduced skeletal muscle ERα and ERβ nuclear protein. Short-term E2 treatment did not change nuclear ERα or ERβ, but decreased cytosolic ERα, so the proportion of ERα in the nucleus compared with the cytosol tended to increase. There was a group-by-treatment interaction (P < 0.05) for nuclear proliferator-activated receptor γ co-activator 1-α and phosphorylated adenosine monophosphate-activated protein kinase, such that E2 increased these proteins in EPM, but decreased these proteins in LPM.
  
  
  CONCLUSIONS
  These preliminary studies of skeletal muscle from early and late postmenopausal women treated with E2 suggest there may be declines in skeletal muscle ER and changes in the E2-mediated regulation of cellular energy homeostasis with increasing time since menopause.
authors.affiliation: 1Division of Geriatric Medicine 2Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 3VA Eastern Colorado Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, CO 4Denver Health and Hospital Authority, Denver, CO 5School of Kinesiology, University of Minnesota, Minneapolis, MN.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Rocio I
authors.initials: RI
authors.lastname: Pereira
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Erickson
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Swibas
authors.forename: Chounghun
authors.initials: C
authors.lastname: Kang
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Van Pelt
mesh_terms: D000368:Aged; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D017698:Postmenopause / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D017868:Cyclic AMP-Dependent Protein Kinases