The steroidogenic acute regulatory protein is induced by angiotensin II and K+ in H295R adrenocortical cells

Although the role of arachidonic acid (AA) in angiotensin II (ANG II)- and potassium-stimulated steroid production in zona glomerulosa cells is well documented, the mechanism responsible for AA release is not fully described. In this study we evaluated the mechanism involved in the release of intramitochondrial AA and its role in the regulation of aldosterone synthesis by ANG II in glomerulosa cells. We show that ANG II and potassium induce the expression of acyl-coenzyme A (CoA) thioesterase 2 and acyl-CoA synthetase 4, two enzymes involved in intramitochondrial AA generation/export system well characterized in other steroidogenic systems. We demonstrate that mitochondrial ATP is required for AA generation/export system, steroid production, and steroidogenic acute regulatory protein induction. We also demonstrate the role of protein tyrosine phosphatases regulating acyl-CoA synthetase 4 and steroidogenic acute regulatory protein induction, and hence ANG II-stimulated aldosterone synthesis.

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Expression of the steroidogenic acute regulatory protein mRNA in adrenal tumors and cultured adrenal cells

Journal of Endocrinology ◽

10.1677/joe.0.1500043 ◽

1996 ◽

Vol 150 (1) ◽

pp. 43-50 ◽

Cited By ~ 72

Author(s):

J Liu ◽

P Heikkilä ◽

A I Kahri ◽

R Voutilainen

Keyword(s):

Kinase Inhibitor ◽

Regulatory Protein ◽

Early Response ◽

Steroidogenic Acute Regulatory Protein ◽

Adrenal Tumors ◽

Adrenocortical Cells ◽

Mrna Accumulation ◽

Chain Cleavage ◽

Steroidogenic Acute Regulatory ◽

Adrenocortical Carcinomas

Abstract The steroidogenic acute regulatory protein (StAR) has recently been shown to be a factor necessary for cholesterol transport into adrenal and gonadal mitochondria, which is the regulated, rate-limiting step in steroidogenesis. We show here that StAR mRNA is highly expressed in normal adult adrenals (n=9), adrenocortical adenomas (n=16), adrenal hyperplasias (n=6), adrenocortical carcinomas (n=6) and adrenals adjacent to tumor tissues (n=9). There was a good correlation between the expression of StAR and the cholesterol side-chain cleavage enzyme/20,22-desmolase (P450 scc) mRNAs both in normal (r=0·93; P<0·01) and in tumor (r=0·97; P<0·001) tissues. No StAR mRNA was detected in Northern blots of liver, kidney, breast, parathyroid or phaeochromocytoma RNAs. In cultured adrenocortical cells, adrenocorticotropin (ACTH), (Bu)2cAMP, and cholera toxin increased StAR and P450 scc mRNA accumulation 6- to 18-fold, dose-and time-dependently. StAR (and P450 scc) mRNA increased relatively slowly in response to ACTH treatment, with the maximal increment at 24 h, while the mRNA of the early response gene c-fos peaked within 2 h. The protein kinase inhibitor H-7 inhibited basal and ACTH-induced StAR mRNA expression. Our results show that StAR mRNA is expressed at high levels in normal human adrenals and adrenocortical neoplasms. It is up-regulated in parallel with P450 scc by ACTH in adult adrenocortical cells, which suggests that ACTH is at least one of the key regulators of adrenal StAR expression. Journal of Endocrinology (1996) 150, 43–50

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

Endocrine ◽

10.1007/s12020-007-9030-1 ◽

2007 ◽

Vol 32 (2) ◽

pp. 155-165 ◽

Cited By ~ 2

Author(s):

Wei-Ping Fon ◽

Pi-Hsueh S. Li

Keyword(s):

Gene Expression ◽

Protein Gene ◽

Regulatory Protein ◽

Histone H3 ◽

Steroidogenic Acute Regulatory Protein ◽

Adrenocortical Cells ◽

Histone H3 Acetylation ◽

Steroidogenic Acute Regulatory ◽

H3 Acetylation

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Inheritable stimulatory effects of caffeine on steroidogenic acute regulatory protein expression and cortisol production in human adrenocortical cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2011.11.001 ◽

2012 ◽

Vol 195 (1) ◽

pp. 68-75 ◽

Cited By ~ 18

Author(s):

Jie Ping ◽

You-ying Lei ◽

Lian Liu ◽

Ting-ting Wang ◽

Ying-hong Feng ◽

...

Keyword(s):

Protein Expression ◽

Regulatory Protein ◽

Steroidogenic Acute Regulatory Protein ◽

Adrenocortical Cells ◽

Steroidogenic Acute Regulatory

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A Genome-Wide Expression Profile of Adrenocortical Cells in Knockout Mice Lacking Steroidogenic Acute Regulatory Protein

Endocrinology ◽

10.1210/en.2011-1627 ◽

2012 ◽

Vol 153 (6) ◽

pp. 2714-2723 ◽

Cited By ~ 9

Author(s):

Tomohiro Ishii ◽

Toshikatsu Mitsui ◽

Sadafumi Suzuki ◽

Yumi Matsuzaki ◽

Tomonobu Hasegawa

Keyword(s):

Expression Profile ◽

Adrenal Glands ◽

Fluorescent Protein ◽

Cholesterol Biosynthesis ◽

Regulatory Protein ◽

Steroidogenic Acute Regulatory Protein ◽

P Value ◽

Adrenocortical Cells ◽

A Genome ◽

Steroidogenic Acute Regulatory

Steroidogenic acute regulatory protein (StAR) facilitates cholesterol transfer into the inner mitochondrial membrane in the acute phase of steroidogenesis. Mice lacking StAR (Star−/−) share phenotypes with human individuals having congenital lipoid adrenal hyperplasia including compromised production of steroid hormones and florid accumulation of cholesterol esters in adrenal glands and gonads. To define a specific pattern of molecular changes with StAR deficiency, we performed transcriptome analysis of adrenal cells selectively isolated by fluorescent-activated cell sorting at embryonic d 17.5 or 18.5 in seven wild-type (Star+/+) or four Star−/− mice having the transgene targeting the enhanced green fluorescent protein to cell lineages that express StAR. A gene expression profile was obtained by whole-mouse genome microarray and confirmed by quantitative real-time PCR, identifying 1206 and 767 significantly up-regulated and down-regulated genes, respectively, in Star−/− mice compared with Star+/+ mice (fold difference ≥ 2 and P value < 0.05 with false discovery rate < 0.2). In Star−/− mice, expression levels of genes involved in cholesterol efflux and the inflammatory response were significantly up-regulated, whereas those related to steroid hormone biosynthesis or cholesterol biosynthesis and influx were not significantly changed. Immunoreactive Iba1 or F4/80 (macrophage marker) in adrenal glands of Star−/− mice was detected not only in an increased number of resident macrophages but also in most adrenocortical cells. These findings expand our understanding of the pathophysiology of adrenal glands with the disruption of StAR and propose a reciprocal interaction between adrenocortical cells and resident macrophages inside adrenal glands of Star−/− mice.

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