Hotta M, Baird A
Proc Natl Acad Sci U S A. 1986 Oct;83(20):7795-9. doi: 10.1073/pnas.83.20.7795.
Transforming growth factor type beta (TGF-beta) suppresses basal as well as corticotropin (ACTH)-stimulated steroid formation by bovine adrenocortical cells in culture. The effect is dose dependent and is not accompanied by any change in adrenocortical cell growth. The minimum effective dose of TGF-beta is 4 X 10(-13) M (10 pg/ml), and maximal inhibition is observed at a concentration of 4 X 10(-11) M (1 ng/ml). A 16- to 20-hr incubation with TGF-beta is required to decrease steroidogenesis, and 12-18 hr are required before cells treated with TGF-beta recover complete responsiveness to corticotropin. Increases in cAMP mediated by corticotropin, forskolin, and isobutylmethylxanthine are not modified by the addition of TGF-beta; thus adenylate cyclase activity is unaffected by TGF-beta. Although TGF-beta inhibits the formation of all of the delta 4-steroids measured (including cortisol, corticosterone, aldosterone, and androstenedione), its effect can be completely reversed by the addition of 25-hydroxycholesterol, pregnenolone, or progesterone to the cells. In contrast, the addition of low density lipoprotein has no effect suggesting that TGF-beta targets the conversion of cholesterol precursors to cholesterol. The results demonstrate a highly potent effect of TGF-beta on the differentiated function of the adrenocortical cell. The inhibition of steroidogenesis can be dissociated from any effect on cell proliferation, and it occurs distal to the formation of cAMP but proximal to the formation of cholesterol. The results suggest that in the adrenal, TGF-beta or TGF-beta-like proteins may be playing an important role in modifying the differentiated state of the adrenocortical cell.
转化生长因子β（TGF-β）可抑制培养的牛肾上腺皮质细胞的基础类固醇生成以及促肾上腺皮质激素（ACTH）刺激的类固醇生成。该作用具有剂量依赖性，且不伴随肾上腺皮质细胞生长的任何变化。TGF-β的最小有效剂量为4×10⁻¹³ M（10 pg/ml），在4×10⁻¹¹ M（1 ng/ml）的浓度下观察到最大抑制作用。需要与TGF-β孵育16至20小时才能降低类固醇生成，在用TGF-β处理的细胞恢复对促肾上腺皮质激素的完全反应性之前需要12至18小时。促肾上腺皮质激素、福斯可林和异丁基甲基黄嘌呤介导的cAMP增加不会因添加TGF-β而改变；因此腺苷酸环化酶活性不受TGF-β影响。尽管TGF-β抑制所测量的所有δ4-类固醇（包括皮质醇、皮质酮、醛固酮和雄烯二酮）的形成，但向细胞中添加25-羟胆固醇、孕烯醇酮或孕酮可完全逆转其作用。相比之下，添加低密度脂蛋白没有效果，这表明TGF-β靶向胆固醇前体向胆固醇的转化。结果表明TGF-β对肾上腺皮质细胞的分化功能具有高效作用。类固醇生成的抑制可与对细胞增殖的任何作用分离，并且它发生在cAMP形成的远端但胆固醇形成的近端。结果表明，在肾上腺中，TGF-β或TGF-β样蛋白可能在调节肾上腺皮质细胞的分化状态中起重要作用。
