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Domest Anim Endocrinol. 2008 Jul;35(1):88-97. Epub 2008 Mar 24.
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.
Kamanga-Sollo E, White ME, Hathaway MR, Chung KY, Johnson BJ, Dayton WR.
Animal Growth and Development Laboratory, Department of Animal Science, University of Minnesota, 348 Andrew Boss Laboratory, 1354 Eckles Avenue, St. Paul, MN 55108, USA.
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.
My notes:
Satellite cells are skeletal muscle progenitor cells, meaning cells responsible for muscle hyperplasia (increase in # of muscle fibers). Satellite cells were cultured in plastic dishes and fed either a combination of TA + E2, E2 only, or TA only. Initially, the authors detected an elevetaed expression of IGF1 gene expression, which indicates that these agents promote IGF1 production which may in turn would promote muscle hyperplasia. However, this was not the case since hyperplasia occured in the presence of IGF1 binding protein added to the cultures. Therefore, the data suggests that TA may promote increase in # muscle cells independent of IGF1 action. Blocking either the E2 receptor or the androgen receptor knocked out the effect of increasing # of satellite cells. However, please keep in mind that: 1) this is my interpretation of results, and 2) that these are cultured cells and that the effects in vivo could be quite different.
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.
Kamanga-Sollo E, White ME, Hathaway MR, Chung KY, Johnson BJ, Dayton WR.
Animal Growth and Development Laboratory, Department of Animal Science, University of Minnesota, 348 Andrew Boss Laboratory, 1354 Eckles Avenue, St. Paul, MN 55108, USA.
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.
My notes:
Satellite cells are skeletal muscle progenitor cells, meaning cells responsible for muscle hyperplasia (increase in # of muscle fibers). Satellite cells were cultured in plastic dishes and fed either a combination of TA + E2, E2 only, or TA only. Initially, the authors detected an elevetaed expression of IGF1 gene expression, which indicates that these agents promote IGF1 production which may in turn would promote muscle hyperplasia. However, this was not the case since hyperplasia occured in the presence of IGF1 binding protein added to the cultures. Therefore, the data suggests that TA may promote increase in # muscle cells independent of IGF1 action. Blocking either the E2 receptor or the androgen receptor knocked out the effect of increasing # of satellite cells. However, please keep in mind that: 1) this is my interpretation of results, and 2) that these are cultured cells and that the effects in vivo could be quite different.