Feige J J, Cochet C, Savona C, Shi D L, Keramidas M, Defaye G, Chambaz E M
INSERM Unité 244, Centre d'Etudes Nucléaires, Grenoble, France.
Endocr Res. 1991;17(1-2):267-79. doi: 10.1080/07435809109027201.
Transforming growth factor beta 1 (TGF beta 1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGF beta 1, TGF beta 2, TGF beta 3, TGF beta 4 and TGF beta 5) and functionally distinct proteins. In the past few years, TGF beta 1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroidogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGF beta 1 on bovine adrenocortical cell (zona fasciculata-reticularis) functions. We identified the steroid 17 alpha-hydroxylase (P-450 17 alpha) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGF beta 1 in these cells. We characterized TGF beta 1 receptors at the surface of adrenocortical cells (mainly type I and type III receptors) and observed that their number is increased under ACTH treatment. Furthermore, we could detect the presence of immunoreactive TGF beta 1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2-macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum. Taken together, these observations led us to a working hypothesis, proposing TGF beta 1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGF beta 1 complex as the important limiting step controlling its action in the adrenal cortex.
转化生长因子β1（TGFβ1）是一个结构相关的调节多肽大家族的成员，该家族包括功能相似的蛋白质（TGFβ1、TGFβ2、TGFβ3、TGFβ4和TGFβ5）以及功能不同的蛋白质。在过去几年中，TGFβ1已成为一种多功能蛋白质。其显著特性之一是它能够负向调节分化的、产生类固醇的肾上腺皮质功能。在此，我们综述了我们最近关于TGFβ1对牛肾上腺皮质细胞（束状带-网状带）功能影响的研究结果。我们确定类固醇17α-羟化酶（P-450 17α）生物合成酶和血管紧张素II受体是主要靶点，其表达在这些细胞中受到TGFβ1的负向调节。我们对肾上腺皮质细胞表面的TGFβ1受体（主要是I型和III型受体）进行了表征，并观察到在促肾上腺皮质激素（ACTH）处理下它们的数量增加。此外，我们能够在牛肾上腺皮质中检测到免疫反应性TGFβ1，而在肾上腺髓质和被膜中则无法检测到。我们还观察到肾上腺皮质细胞以潜伏形式分泌TGFβ1，同时分泌大量α2-巨球蛋白，α2-巨球蛋白是一种已知与血清中TGFβ的潜伏状态有关的蛋白酶抑制剂。综上所述，这些观察结果使我们提出了一个工作假说，即TGFβ1是肾上腺皮质类固醇生成功能的自分泌和/或旁分泌调节因子。这一概念指出，潜伏性TGFβ1复合物的生理激活是控制其在肾上腺皮质中作用的重要限制步骤。
