A genome-wide expression profile of adrenocortical cells in knockout mice lacking steroidogenic acute regulatory protein

Tomohiro Ishii, Toshikatsu Mitsui, Sadafumi Suzuki, Yumi Matsuzaki, Tomonobu Hasegawa

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2714-2723
Number of pages10
JournalEndocrinology
Volume153
Issue number6
DOIs
Publication statusPublished - 2012 Jun

Fingerprint

Knockout Mice
Genome
Adrenal Glands
Macrophages
Cholesterol
Steroids
Hormones
Protein Deficiency
Cholesterol Esters
Gonads
Mitochondrial Membranes
Gene Expression Profiling
Cell Lineage
steroidogenic acute regulatory protein
Transgenes
Transcriptome
Real-Time Polymerase Chain Reaction
Phenotype
Gene Expression
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

A genome-wide expression profile of adrenocortical cells in knockout mice lacking steroidogenic acute regulatory protein. / Ishii, Tomohiro; Mitsui, Toshikatsu; Suzuki, Sadafumi; Matsuzaki, Yumi; Hasegawa, Tomonobu.

In: Endocrinology, Vol. 153, No. 6, 06.2012, p. 2714-2723.

Research output: Contribution to journalArticle

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