转化生长因子-β对人卵巢卵泡膜样肿瘤细胞模型中类固醇生成及关键类固醇生成酶表达的影响

The effect of transforming growth factor-beta on steroidogenesis and expression of key steroidogenic enzymes with a human ovarian thecal-like tumor cell model.

作者信息

Carr B R, McGee E A, Sawetawan C, Clyne C D, Rainey W E

机构信息

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, 75235-9032, USA.

出版信息

Am J Obstet Gynecol. 1996 Apr;174(4):1109-16; discussion 1116-7. doi: 10.1016/s0002-9378(96)70652-x.

DOI:10.1016/s0002-9378(96)70652-x

PMID:8623837

Abstract

OBJECTIVE

Our purpose was to determine the effects of transforming growth factor-beta on steroidogenesis and regulation of steroidogenic enzyme expression by use of a human ovarian thecal-like tumor cell culture system.

STUDY DESIGN

Human ovarian thecal-like tumor cells were treated in serum-free medium in the presence or absence of forskolin and transforming growth factor-beta 1. The accumulation of progesterone and androstenedione in the culture medium was evaluated by radioimmunoassay. The effects of forskolin with or without transforming growth factor-beta 1 on the enzymatic activity of P450c17 and 3 beta HSD, the expression of immunodetectable P450c17 protein, and the expression of messenger ribonucleic acid for P450scc, P450c17, and 3 beta HSD were determined.

RESULTS

Basal steroid secretion, steroidogenic enzyme activity, enzyme protein, and messenger ribonucleic acid expression were not affected by transforming growth factor-beta 1 alone. Forskolin treatment significantly stimulated steroid production and the enzymatic activity of P450c17 and 3 beta HSD up to 10-fold above basal levels. However, transforming growth factor-beta 1 inhibited forskolin-stimulated androstenedione production to near basal levels and increased progesterone 1.4- to 2-fold while suppressing P450c17 enzyme activity to near basal levels, but it did not affect 3 beta HSD activity. Forskolin-stimulated immunodetectable P450c17 alpha protein was markedly inhibited by transforming growth factor-beta 1. In addition, transforming growth factor-beta 1 markedly inhibited the forskolin-stimulation of P450c17 messenger ribonucleic acid, while not significantly altering P450scc or 3 beta HSD messenger ribonucleic acid expression.

CONCLUSION

Forskolin stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17 and 3 beta HSD activity, immunodetectable P450c17, and messenger ribonucleic acid content for P450scc, P450c17, and 3 beta HSD. Transforming growth factor-beta 1 inhibited forskolin stimulation of androstenedione production through the inhibition of P450c17 expression.

摘要

目的

我们的目的是利用人卵巢类卵泡膜细胞瘤细胞培养系统来确定转化生长因子-β对类固醇生成及类固醇生成酶表达调控的影响。

研究设计

在有无福斯高林和转化生长因子-β1的情况下，将人卵巢类卵泡膜细胞瘤细胞在无血清培养基中进行处理。通过放射免疫分析法评估培养基中孕酮和雄烯二酮的积累情况。测定了有无转化生长因子-β1时福斯高林对P450c17和3βHSD酶活性、可免疫检测的P450c17蛋白表达以及P450scc、P450c17和3βHSD信使核糖核酸表达的影响。

结果

基础类固醇分泌、类固醇生成酶活性、酶蛋白和信使核糖核酸表达不受单独的转化生长因子-β1影响。福斯高林处理显著刺激类固醇生成以及P450c17和3βHSD的酶活性，使其比基础水平高出10倍。然而，转化生长因子-β1将福斯高林刺激的雄烯二酮生成抑制至接近基础水平，并使孕酮增加1.4至2倍，同时将P450c17酶活性抑制至接近基础水平，但不影响3βHSD活性。转化生长因子-β1显著抑制了福斯高林刺激的可免疫检测的P450c17α蛋白。此外，转化生长因子-β1显著抑制了福斯高林对P450c17信使核糖核酸的刺激，而对P450scc或3βHSD信使核糖核酸表达没有显著改变。