title: Activation of GPR30 improves exercise capacity and skeletal muscle strength in senescent female Fischer344 × Brown Norway rats.
abstract: The molecular mechanisms of muscle weakness and sarcopenia in postmenopausal women are largely unknown. To determine the effect of a new estrogen receptor, GPR30, in the maintenance of exercise capacity and skeletal muscle function in females, the selective GPR30 agonist, G1 (100 μg/kg/day), or vehicle (V, soybean oil) was administered subcutaneously daily (n = 7 per group) to ovariectomized (OVX) 27-month-old Fischer 344 × Brown Norway (F344BN) female rats. Following 8 weeks of treatment, the exercise capacity (treadmill walk time to exhaustion) was reduced in OVX vs. sham rats (5.1 ± 1.4 vs. 11.0 ± 0.9 min, P < 0.05), and chronic G1 restored exercise capacity (12.9 ± 1.2 min; P < 0.05 vs. OVX-V). Similarly, the peak twitch of electrically stimulated soleus muscles was decreased by 22% in OVX vs. sham rats (P < 0.05), and G1 attenuated this decline (P < 0.05). Western blot analysis showed that chronic G1 treatment attenuated OVX-associated decreases in heat shock protein (HSP) 90, HSP70, and HSP27 expressions. In vitro studies using the L6 myoblast cell line demonstrated that G1 increased mRNA levels of HSPs in cultured cells. Collectively, these data demonstrate that the activation of GPR30 mitigates the adverse effects of estrogen loss on exercise capacity and skeletal muscle contractile function in old F344BN rats. The protective effects of GPR30 might be through its upregulation of heat shock proteins in skeletal muscle.
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA. Electronic address: haowang@wakehealth.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Institute of Biomedical Sciences, Drug Development Program, Federal University of Rio de Janeiro, Brazil. Electronic address: allankdc@gmail.com.
authors.forename: Allan
authors.initials: A
authors.lastname: Alencar
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA. Electronic address: mlin@wakehealth.edu.
authors.forename: Marina
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA. Electronic address: xsun@wakehealth.edu.
authors.forename: Xuming
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Institute of Biomedical Sciences, Drug Development Program, Federal University of Rio de Janeiro, Brazil. Electronic address: rtsudo@icb.ufrj.br.
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sudo
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Institute of Biomedical Sciences, Drug Development Program, Federal University of Rio de Janeiro, Brazil. Electronic address: gzsudo@oi.com.br.
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
authors.affiliation: Programs in Rehabilitation Science and Physical Therapy, Dept. of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, USA. Electronic address: lowex017@umn.edu.
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Lowe
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; The Hypertension and Vascular Research Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA; Sticht Center on Aging, Wake Forest School of Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA. Electronic address: lgroban@wakehealth.edu.
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004967:Estrogens / Q000378:metabolism; D005080:Exercise Test; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000502:physiology*; D010052:Ovariectomy; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; C520305:Gper1 protein, rat; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: Exercise capacity; Fischer344 × Brown Norway rat; GPR30; Ovariectomy; Skeletal muscle