促肾上腺皮质激素和细胞因子对人肾上腺细胞中硫酸脱氢表雄酮硫酸转移酶信使核糖核酸的影响。

Effects of ACTH and cytokines on dehydroepiandrosterone sulfotransferase messenger RNA in human adrenal cells.

作者信息

Parker C R, Stankovic A K, Faye-Petersen O, Falany C N, Li H, Jian M

机构信息

Department of Obstetrics and Gynecology, University of Alabama at Birmingham, USA.

出版信息

Endocr Res. 1998 Aug-Nov;24(3-4):669-73. doi: 10.3109/07435809809032668.

DOI:10.3109/07435809809032668

PMID:9888558

Abstract

Dehydroepiandrosterone sulfate (DS) is the major adrenal androgen produced in the fetal and adult human; its formation is dependent upon the action of dehydroepiandrosterone sulfotransferase (DST). Since the factors that regulate DST are poorly characterized, we investigated the effects of ACTH, which stimulates DS production, and the cytokines transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) , both of which are inhibitory to adrenal steroidogenesis, on cultured human fetal adrenal cells. Cellular levels of DST mRNA were increased in a dose dependent fashion in response to ACTH; DST mRNA was less responsive to ACTH stimulation than was 17 hydroxylase (CYP 17) mRNA. The stimulatory effects of ACTH on DST mRNA levels were blunted by both TGF-beta and TNF-alpha; the inhibitory effects of TNF-alpha on DST mRNA were more striking than were those on CYP 17 mRNA. These data suggest that DS production can be altered by several agents acting on the DST gene.

摘要

硫酸脱氢表雄酮（DS）是胎儿和成年人体内产生的主要肾上腺雄激素；其形成依赖于硫酸脱氢表雄酮硫酸转移酶（DST）的作用。由于调节DST的因素尚不明确，我们研究了促肾上腺皮质激素（ACTH）、转化生长因子-β（TGF-β）和肿瘤坏死因子-α（TNF-α）对培养的人胎儿肾上腺细胞的影响，其中ACTH刺激DS生成，而TGF-β和TNF-α均抑制肾上腺类固醇生成。DST mRNA的细胞水平呈剂量依赖性地因ACTH而增加；DST mRNA对ACTH刺激的反应性低于17-羟化酶（CYP 17）mRNA。TGF-β和TNF-α均减弱了ACTH对DST mRNA水平的刺激作用；TNF-α对DST mRNA的抑制作用比对CYP 17 mRNA的抑制作用更显著。这些数据表明，作用于DST基因的几种因子可改变DS的生成。