Oxysterols regulate expression of the steroidogenic acute regulatory protein

S. R. King, A. A. Matassa, E. K. White, L. P. Walsh, Y. Jo, R. M. Rao, D. M. Stocco, Mary E. Reyland

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The steroidogenic acute regulatory (StAR) protein promotes intramitochondrial delivery of cholesterol to the cholesterol side-chain cleavage system, which catalyzes the first enzymatic step in all steroid synthesis. Intriguingly, substrate cholesterol derived from lipoprotein can upregulate, StAR gene expression. Moreover, substrate oxysterols have been suggested to also play a role. To investigate whether oxysterols can regulate StAR expression, two steroidogenic cell lines, mouse Y1 adrenocortical and MA-10 Leydig tumor cells, were treated with various oxysterols and steroids, including 25-hydroxycholesterol (25 OHC), 22(R)OHC and 20αOHC. The majority of these compounds rapidly increased StAR protein levels within as little as 1 h. The most potent oxysterols were 20αOHC for Y1 and 25 OHC for MA-10 cells. After 8 h, StAR mRNA abundance also increased whereas there were no detected changes in promoter activity. Thus, in contrast to lipoprotein, oxysterols acutely increase StAR protein levels independently of mRNA abundance, and later increase mRNA levels independently of new gene transcription. Therefore, we propose that oxysterols modulate steroidogenesis at two levels. First, oxysterols may be important in post-transcriptional regulation of StAR activity and production of steroids for paracrine action. Secondly, through direct conversion to steroid, oxysterols may account in part for StAR-independent steroid production in the body.

Original languageEnglish (US)
Pages (from-to)507-517
Number of pages11
JournalJournal of molecular endocrinology
Volume32
Issue number2
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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