Effects of transforming growth factor beta on ovine adrenocortical cells.
Effects of transforming growth factor beta on ovine adrenocortical cells.
复制标题
转化生长因子β对绵羊肾上腺皮质细胞的影响。
DOI：
10.1016/0303-7207(88)90178-5
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发表时间：
1988
影响因子：
4.1
通讯作者：
Saez,JM
中科院分区：
文献类型：
--
作者：
Rainey,WE;Viard,I;Mason,JI;Cochet,C;Chambaz,EM;Saez,JM
转化生长因子β (TGFβ)是一种强有力的类固醇细胞功能调节剂。然而，其作用机制尚不清楚。我们研究了TGFβ对绵羊肾上腺皮质（OAC）细胞原代培养的作用。OAC细胞对TGFβ具有高亲和力受体（KD≈- 7.6±1.5 ×l6−11M）。此外，tgf - β还能抑制肾上腺皮质功能的以下标志物：(1)ACTH、霍乱毒素和forskolin对cAMP和类固醇生成的急性刺激；(2)急性8-溴camp刺激皮质类固醇和孕烯醇酮的产生；(3) p -450 17α-羟化酶蛋白的活性和数量以及11β-和21-羟化酶的活性。TGFβ对acth诱导的cAMP和类固醇产生的抑制作用具有时间依赖性（分别在6和3 h抑制一半）和剂量依赖性（ID50= 10-12M）。根据这些数据，我们得出结论，tgf - β在cAMP产生前后迅速作用于OAC细胞对ACTH刺激的急性反应位点。当添加易于渗透的胆固醇衍生物22r -羟基胆固醇刺激类固醇生成时，这些细胞中的孕烯醇酮生成不受tgf - β的抑制。因此，对OAC细胞的快速影响是通过tgf - β作用于细胞内胆固醇池的利用，以急性刺激类固醇的形成，而不是直接作用于胆固醇侧链切割酶。此外，在缺乏或存在脂蛋白的情况下（长达36小时），ACTH刺激的细胞对TGFβ的抑制作用敏感。综上所述，这些数据放大了TGFβ对肾上腺皮质细胞功能的多效性作用，并证明了TGFβ的一个急性作用是利用内源性胆固醇供应来生产类固醇。
Transforming growth factor beta (TGFβ) is a potent regulator of steroidogenic cell function. However, the mechanisms of the effects are not well understood. We studied the actions of TGFβ on primary cultures of ovine adrenocortical (OAC) cells. OAC cells had high affinity receptors for TGFβ (KD≈- 7.6 ± 1.5 ×l6−11M). In addition, TGFβ inhibited the following markers of adrenocortical function: (1) ACTH, cholera toxin and forskolin acute stimulation of cAMP and steroid production; (2) the acute 8-bromo-cAMP stimulation of corticosteroid and pregnenolone production; and (3) the activity and amount ofP-450 17α-hydroxylase protein as well as activities of 11β- and 21-hydroxylases. The inhibitory effects of TGFβ on ACTH-induced cAMP and steroid production were time (half inhibition at 6 and 3 h respectively) and dose dependent (ID50= 10-12M). From these data we concluded that TGFβ acted rapidly on sites of OAC cell acute responses to stimulation by ACTH before and after the production of cAMP. Pregnenolone production in these cells was not inhibited by TGFβ when steroid production was stimulated on the addition of the readily permeable cholesterol derivative, 22R-hydroxycholesterol. Thus, the rapid effect on OAC cells was manifest by TGFβ action on the utilization of cellular pools of cholesterol for the acute stimulation of steroid formation and not by direct action on the cholesterol side-chain cleavage enzyme. In addition, cells stimulated with ACTH in the absence or presence of lipoproteins (for up to 36 h) were susceptible to the inhibitory action of TGFβ. Taken together, these data amplify the pleiotropic actions of TGFβ on adrenocortical cell function and demonstrate that one acute action of TGFβ is on the utilization of endogenous supplies of cholesterol for steroid production.