Ferraz-de-Souza, B;
Hudson-Davies, RE;
Lin, L;
Parnaik, R;
Hubank, M;
Dattani, MT;
Achermann, JC;
(2011)
Sterol O-Acyltransferase 1 (SOAT1, ACAT) Is a Novel Target of Steroidogenic Factor-1 (SF-1, NR5A1, Ad4BP) in the Human Adrenal.
The Journal of Clinical Endocrinology & Metabolism
, 96
(4)
E663 - E668.
10.1210/jc.2010-2021.
![[thumbnail of E663.full.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
E663.full.pdf Available under License : See the attached licence file. Download (881kB) |
Abstract
Context: Steroidogenic factor-1 (SF-1, NR5A1, Ad4BP) is a master regulator of adrenal development and steroidogenesis. Defects in several known targets of SF-1 can cause adrenal disorders in humans.Objective: We aimed to identify novel targets of SF-1 in the human adrenal. These factors could be important regulators of adrenal development and steroidogenesis and potential candidates for adrenal dysfunction.Design: A gene discovery strategy was developed based on bidirectional manipulation of SF-1. Overexpression or knockdown of SF-1 in NCI-H295R human adrenocortical cells was used to identify a subset of positively-regulated SF-1 targets.Results: This approach identified well-established SF-1 target genes (STAR, CYP11A) and several novel genes (VSNL1, ZIM2, PEG3, SOAT1, and MTSS1). Given its role in cholesterol metabolism, sterol O-acyltransferase 1 (SOAT1, previously referred to as acyl-Coenzyme A: cholesterol acyltransferase 1, ACAT) was studied further and found to be expressed in the developing human fetal adrenal cortex. We hypothesized that impaired SOAT1 activity could result in adrenal insufficiency through reduced cholesteryl ester reserves or through toxic destruction of the adrenal cells during development. Therefore, mutational analysis of SOAT1 in a cohort of 43 patients with unexplained adrenal insufficiency was performed but failed to reveal significant coding sequence changes.Conclusions: Our reverse discovery approach led to the identification of novel SF-1 targets and defined SOAT1 as an important factor in human adrenal steroidogenesis. SF-1-dependent upregulation of SOAT1 may be important for maintaining readily-releasable cholesterol reserves needed for active steroidogenesis and during episodes of recurrent stress. (J Clin Endocrinol Metab 96: E663-E668, 2011)
| Type: | Article |
|---|---|
| Title: | Sterol O-Acyltransferase 1 (SOAT1, ACAT) Is a Novel Target of Steroidogenic Factor-1 (SF-1, NR5A1, Ad4BP) in the Human Adrenal |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1210/jc.2010-2021 |
| Publisher version: | http://dx.doi.org/10.1210/jc.2010-2021 |
| Language: | English |
| Additional information: | © 2011 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | CHOLESTEROL ACYLTRANSFERASE, ACYL-COENZYME, GENE, MUTATION, INHIBITION, EXPRESSION, FAILURE, DISEASE, BINDING, MICE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/762804 |
Archive Staff Only
 |
View Item |
