Keramidas M, Chambaz E M, Feige J J
Unité INSERM 244, Laboratoire de Biochimie des Régulations Cellulaires Endocrines, Grenoble, France.
Mol Cell Endocrinol. 1992 Apr;84(3):243-51. doi: 10.1016/0303-7207(92)90035-5.
alpha 2-Macroglobulin (alpha 2M) is the major protein secreted by bovine adrenocortical cells in primary culture and its synthesis is stimulated by transforming growth factor beta (TGF beta). We investigated here the effects of alpha 2M on adrenocortical steroidogenesis. We observed that commercial preparations of bovine plasma alpha 2M were able to mimic the inhibitory action of TGF beta on adrenocortical cortisol production, with the same specificity of action directed at the steroid 17 alpha-hydroxylation step. This inhibition was time-dependent and dose-dependent (50% inhibition observed with 2 mg/ml alpha 2M). Acid/ethanol extracts of alpha 2M appeared to retain the full inhibitory activity of alpha 2M. Anti-TGF beta antibodies could reverse the inhibition caused by the acid/ethanol extract but not that caused by native alpha 2M. Taken together, these results indicate that the inhibition of adrenocortical steroidogenesis induced by alpha 2M is caused by associated TGF beta. We estimated that 2 mg of alpha 2M contained approximately 0.1 ng of TGF beta, corresponding to a molar ratio of 1/700,000 between TGF beta and alpha 2M. These results also clearly indicate that the alpha 2M-TGF beta complexes are biologically active on adrenocortical cells, suggesting that these cells possess the enzymatic equipment that can activate the latent alpha 2M-TGF beta complexes.
α2-巨球蛋白（α2M）是原代培养的牛肾上腺皮质细胞分泌的主要蛋白质，其合成受转化生长因子β（TGFβ）刺激。我们在此研究了α2M对肾上腺皮质类固醇生成的影响。我们观察到，牛血浆α2M的商业制剂能够模拟TGFβ对肾上腺皮质皮质醇产生的抑制作用，其作用特异性相同，均针对类固醇17α-羟化步骤。这种抑制作用具有时间依赖性和剂量依赖性（2mg/ml的α2M可观察到50%的抑制率）。α2M的酸/乙醇提取物似乎保留了α2M的全部抑制活性。抗TGFβ抗体可逆转酸/乙醇提取物引起的抑制作用，但不能逆转天然α2M引起的抑制作用。综上所述，这些结果表明，α2M诱导的肾上腺皮质类固醇生成抑制是由相关的TGFβ引起的。我们估计，2mg的α2M含有约0.1ng的TGFβ，TGFβ与α2M的摩尔比为1/700,000。这些结果还清楚地表明，α2M-TGFβ复合物对肾上腺皮质细胞具有生物活性，这表明这些细胞具备能够激活潜在α2M-TGFβ复合物的酶系。
