CORTICOTROPIN REGULATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE-DELTA-S-]4-ISOMERASE IN OVINE ADRENOCORTICAL-CELLS - INHIBITION BY TRANSFORMING GROWTH-FACTOR-BETA

被引:43
作者
NAVILLE, D
RAINEY, WE
MASON, JI
机构
[1] UNIV TEXAS,SW MED CTR,CECIL H & IDA GREEN CTR REPROD BIOL SCI,DALLAS,TX 75235
[2] UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235
关键词
3-BETA-HYDROXYSTEROID DEHYDROGENASE; TRANSFORMING GROWTH FACTOR -BETA (OVINE); (ADRENOCORTICAL CELLS);
D O I
10.1016/0303-7207(91)90168-R
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In the steroidogenic pathway, 3-beta-hydroxysteroid dehydrogenase/isomerase (3-beta-HSD) is a key enzyme which controls the formation of DELTA-4-3-ketosteroids from DELTA-5-3-beta-hydroxysteroids. Herein, we used primary cultures of ovine adrenocortical (OAC) cells to study the effects of ACTH and transforming growth factor beta (TGF-beta) on 3-beta-HSD activity, protein and mRNA levels. TGF-beta has been previously reported to be a potent inhibitor of steroid formation in OAC cells. By using an antibody against human placental 3-beta-HSD, we showed that ACTH-treatment had a dose- and time-dependent stimulatory effect on 3-beta-HSD protein amount. This effect was maximal using 10(-9) M ACTH after a 48 h treatment. When included in the treatment medium, TFG-beta inhibited this stimulation by ACTH in a dose- and time-dependent manner. We also used a human 3-beta-HSD cDNA probe to demonstrate that the effect of both ACTH and TFG-beta were exerted at the mRNA level with maximal effects observed using 10(-9) M for ACTH and 1 ng/ml for TGF-beta. Bu2cAMP mimicked the effects of ACTH, and TGF-beta had an inhibitory effect on this stimulation. It appears from these data that TGF-beta is a negative regulator of 3-beta-HSD expression in OAC cells. The inhibitory effect of TGF-beta on 3-beta-HSD was contrasted to the TGF-beta effect on 17-alpha-hydroxylase cytochrome P-450 (P-450(17-alpha)). While the levels of both enzymes decreased, that of 3-beta-HSD was less sensitive than that of P-450(17-alpha) which decreased following TGF-beta treatment to non-detectable levels. The different sensitivities of steroidogenic enzymes to factors which regulate growth and differentiation such as TGF-beta may play a role in determining the nature of steroids released from adrenocortical cells.
引用
收藏
页码:257 / 263
页数:7
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