Kamanga-Sollo E, White M E, Hathaway M R, Chung K Y, Johnson B J, Dayton W R
Animal Growth and Development Laboratory, Department of Animal Science, University of Minnesota, 348 Andrew Boss Laboratory, 1354 Eckles Avenue, St. Paul, MN 55108, USA.
Domest Anim Endocrinol. 2008 Jul;35(1):88-97. doi: 10.1016/j.domaniend.2008.02.003. Epub 2008 Mar 24.
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.
尽管大量研究表明，雄激素和雌激素类甾体均可提高阉牛的肌肉生长速度和效率，但其作用机制却几乎没有定论。在含有10%胎牛血清（FBS）的培养基中，联合植入17β-雌二醇（E2）/醋酸群勃龙（TBA）可使肌肉IGF-I mRNA显著增加，并且E2和TBA均可刺激牛卫星细胞（BSC）培养物中的IGF-I mRNA水平显著升高。因此，IGF-I表达增加可能在合成代谢类固醇增强的肌肉生长中发挥作用。然而，尽管在含有1%无IGFBP-3猪血清（SS）的培养基中用E2或TBA处理培养的BSC可导致增殖增加，但对IGF-I mRNA表达没有影响，这表明IGF-I表达增加可能不是合成代谢类固醇增强BSC增殖的原因。为了进一步研究雌激素、雄激素和IGF-I受体及其各自配体在E2和TBA刺激的BSC增殖中的作用，我们评估了特异性抑制剂对E2或TBA刺激的BSC增殖的影响。ICI 182 780（一种雌激素受体阻滞剂）和氟他胺（一种雄激素受体抑制剂）分别抑制（p<0.05）E2和TBA刺激的BSC增殖。JB1（一种IGF-I与I型IGF受体结合的竞争性抑制剂）降低（p<0.05）了BSC培养物中E2和TBA刺激的增殖。Raf-1/丝裂原活化蛋白激酶（MEK）1/2/细胞外信号调节激酶1/2以及磷脂酰肌醇3-激酶（PI3K）/Akt信号通路在IGF-I对成肌细胞增殖和分化的作用中均发挥重要作用。MAPK信号通路抑制剂PD98059和PI3K信号通路抑制剂渥曼青霉素均抑制（p<0.05）E2和TBA刺激的培养BSC增殖。我们的数据表明，即使在IGF-I表达未增加的情况下，IGF-I在E2和TBA刺激的培养BSC增殖中也发挥作用。
