Inhibition of transcription affects synthesis of steroidogenic acute regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor cells.

Abstract:

:Hormonal induction of steroidogenesis in the adrenal and gonads is dependent on the synthesis and function of the steroidogenic acute regulatory protein (StAR). As a first approach to investigate the role of translation in the control of StAR expression, we examined StAR protein synthesis and steroid production in MA-10 mouse Leydig tumor cells in the presence of the transcriptional inhibitor, actinomycin D. We show that human CG (hCG)-induced StAR synthesis, as determined by radiolabeling MA-10 cells with [35S]methionine and immunoprecipitation of StAR, is blocked by actinomycin D. The rate of hCG-stimulated progesterone production is also decreased, but not completely blocked, suggesting a possible StAR-independent mechanism that may contribute approximately 10-20% of the acute steroidogenic potential of the cells. When MA-10 cells were pretreated with hCG to increase StAR messenger RNA levels and then the proteins radiolabeled in the presence of hCG or hCG plus actinomycin D, no difference was observed in the amount of the 30-kDa StAR protein synthesized. However, a 50% increase in the precursor form of StAR protein was detected with hCG treatment alone. These data suggest that ongoing StAR protein synthesis is not inhibited by actinomycin D, but that continued synthesis requires transcriptional activity. Progesterone production was inhibited by actinomycin D in the hCG-pretreated cells, supporting the proposal that maintaining StAR protein synthesis is required for optimal steroid production in MA-10 mouse Leydig tumor cells.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Clark BJ,Combs R,Hales KH,Hales DB,Stocco DM

doi

10.1210/endo.138.11.5535

subject

Has Abstract

pub_date

1997-11-01 00:00:00

pages

4893-901

issue

11

eissn

0013-7227

issn

1945-7170

journal_volume

138

pub_type

杂志文章