Dexamethasone-induced suppression of steroidogenic acute regulatory protein gene expression in mouse Y-1 adrenocortical cells is associated with reduced histone H3 acetylation

Abstract

In this study, we investigated the effect of dexamethasone on the expression of steroidogenic acute regulatory protein (StAR) and the acetylation of histone H3 in mouse Y-1 adrenocortical tumor cells. Treatment of Y-1 cells with increasing concentrations (0.001-50 microg/ml) of dexamethasone for 24 h suppressed 8-Br-cAMP (0.5 mM)-stimulated StAR mRNA and protein levels and progesterone production in a dose-dependent manner. Treatment of Y-1 cells with 8-Br-cAMP (0.5 mM) for 1-24 h resulted in a marked increase in StAR mRNA levels. This increase was associated with an increase in progesterone production. StAR mRNA was down-regulated by dexamethasone at times greater than 3 h. To evaluate dexamethasone effect on the endogenous StAR gene, chromatin immunoprecipitation assays were performed in combination with polymerase chain reaction. 8-Br-cAMP increased histone H3 acetylation within the proximal region of the StAR gene promoter and coincubation with dexamethasone blocked this effect. Dexamethasone had no effect on glucocorticoid receptor mRNA expression. These results demonstrate that dexamethasone repression of 8-Br-cAMP-stimulated StAR gene expression in Y-1 cells is accompanied by reductions in histone H3 acetylation associated with the StAR gene promoter.

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

“…Use of the AAV9 system enabled refined assessment of the effects of reduced GR signalling in approximately half of the adult Leydig cells. It is known that supra- or sub-physiological levels of glucocorticoids can impact Leydig cell function and survival [ 21 , 42 ] and down-regulate the expression of Lhcgr [ 43 ] and steroidogenic transcripts [ 44 ]. However, there is little information regarding a requirement for GR-signalling in adult Leydig cell function.…”

Ectopically Expressed Pro-group X Secretory Phospholipase A2 Is Proteolytically Activated in Mouse Adrenal Cells by Furin-like Proprotein Convertases

“…Although the mechanism has not been completely delineated, GX sPLA 2 appears to negatively regulate adrenal glucocorticoid production through transcriptional suppression of StAR, most likely by reducing the activation of LXR (13). StAR represents the rate-limiting protein in steroid hormone production, and many of the factors known to regulate steroidogenesis, including LXR, have their effect by targeting StAR (16,25,26).…”