The expression of steroidogenic acute regulatory protein (StAR) in bovine adrenocortical cells

1998 ◽  
Vol 24 (3-4) ◽  
pp. 565-569 ◽  
Author(s):  
M. R. Nicol ◽  
H. Wang ◽  
R. Ivell ◽  
S. D. Morley ◽  
S. W. Walker ◽  
...  
Keyword(s):  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Adrenocortical Cells ◽  
Steroidogenic Acute Regulatory

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

1996 ◽  
Vol 150 (1) ◽  
pp. 43-50 ◽  
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

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

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2714-2723 ◽  
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 &lt; 0.05 with false discovery rate &lt; 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.

Acute regulation of the bovine gene for the steroidogenic acute regulatory protein in ovarian theca and adrenocortical cells

2000 ◽  
Vol 24 (1) ◽  
pp. 109-118 ◽  
Author(s):  
R Ivell ◽  
G Tillmann ◽  
H Wang ◽  
M Nicol ◽  
PM Stewart ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Cell Cultures ◽  
Protein Biosynthesis ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Mrna Levels ◽  
Adrenocortical Cells ◽  
Theca Cells ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Upregulation of the steroidogenic acute regulatory protein (StAR) is implicated in the rapid synthesis and secretion of steroidogenic cells to produce steroids in response to stimulation by trophic hormones of the gonadal and stress axes. In the present study, we have assessed the kinetics of both StAR gene transcription and protein biosynthesis in primary cell cultures of bovine adrenocortical and ovarian theca cells, under conditions of acute stimulation by corticotrophin (ACTH) and luteinizing hormone (LH), respectively. In both cell systems, detectable upregulation of StAR gene transcription occurred within 1-2 h, reaching maxima at 4 h (theca cells) or 6 h (adrenocortical cells). mRNA levels returned rapidly to baseline, by 12 h or 24 h, respectively. Specific StAR protein levels were assessed by western blotting using a novel antibody raised against a bovine StAR peptide, and showed a similar fast upregulation, albeit delayed by 1-2 h compared with the mRNA. The response of the cultured theca cells was more acute than that of the adrenocortical cells, possibly reflecting the propensity of the LH receptor to desensitize rapidly, unlike the ACTH receptor. The primary bovine theca cell cultures were also used for fully homologous transfection studies using various deletion promoter-reporter constructs of the bovine StAR gene. Kinetic analysis of the results indicated that the acute transcriptional response resides within the proximal (-315 bp) promoter region, which includes two putative responsive elements for the steroidogenic factor-1. More distal promoter regions may be involved in modulating the specificity of expression by combining enhancer and inhibitory functions.

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