title: Roles of IGF-I and the estrogen, androgen and IGF-I receptors in estradiol-17beta- and trenbolone acetate-stimulated proliferation of cultured bovine satellite cells.
abstract: Although numerous studies have shown that both androgenic and estrogenic steroids increase rate and efficiency of muscle growth in steers, there is little consensus as to their mechanism of action. A combined estradiol 17beta (E2)/trenbolone acetate (TBA) implant causes a significant increase in muscle IGF-I mRNA and both E2 and TBA stimulate a significant increase in IGF-I mRNA level in bovine satellite cell (BSC) cultures in media containing 10% fetal bovine serum (FBS). Consequently, increased IGF-I expression may play a role in anabolic-steroid-enhanced muscle growth. However, even though treatment of cultured BSC with E2 or TBA in media containing 1% IGFBP-3-free swine serum (SS) results in increased proliferation there is no effect on IGF-I mRNA expression, suggesting that increased IGF-I expression may not be responsible for anabolic-steroid-enhanced BSC proliferation. To further examine the role of estrogen, androgen and IGF-I receptors and their respective ligands in E2- and TBA-stimulated BSC proliferation, we assessed the effects of specific inhibitors on E2- or TBA-stimulated proliferation of BSC. Both ICI 182 780 (an estrogen receptor blocker) and flutamide (an inhibitor of androgen receptor) suppressed (p<0.05) E2- and TBA-stimulated BSC proliferation, respectively. JB1 (a competitive inhibitor of IGF-I binding to type I IGF receptor) reduced (p<0.05) both E2- and TBA-stimulated proliferation in BSC cultures. Both the Raf-1/MAPK kinase (MEK)1/2/ERK1/2, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathways play significant roles in the actions of IGF-I on proliferation and differentiation of myogenic cells. PD98059, an inhibitor of the MAPK pathway, and wortmannin, an inhibitor of the PI3K pathway, both suppressed (p<0.05) E2- and TBA-stimulated proliferation of cultured BSC. Our data suggest that IGF-I plays a role in E2- and TBA-stimulated proliferation of cultured BSC even in the absence of increased IGF-I expression.
authors.affiliation: Animal Growth and Development Laboratory, Department of Animal Science, University of Minnesota, 348 Andrew Boss Laboratory, 1354 Eckles Avenue, St. Paul, MN 55108, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kamanga-Sollo
authors.forename: M E
authors.initials: ME
authors.lastname: White
authors.forename: M R
authors.initials: MR
authors.lastname: Hathaway
authors.forename: K Y
authors.initials: KY
authors.lastname: Chung
authors.forename: B J
authors.initials: BJ
authors.lastname: Johnson
authors.forename: W R
authors.initials: WR
authors.lastname: Dayton
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014204:Trenbolone Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D045930:Anabolic Agents; D000730:Androstadienes; D003470:Culture Media; D004965:Estrogen Antagonists; D005419:Flavonoids; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D020929:Mitogen-Activated Protein Kinase Kinases; D014204:Trenbolone Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin