A novel mutation in the steroidogenic acute regulatory protein gene promoter leading to reduced promoter activity

Casal, Andres J; Sinclair, Victoria J P; Capponi, Alessandro M; Nicod, Jérôme; Huynh-Do, Uyen; Ferrari, Paolo (2006). A novel mutation in the steroidogenic acute regulatory protein gene promoter leading to reduced promoter activity. Journal of molecular endocrinology, 37(1), pp. 71-80. Bristol, UK: Journal of Endocrinology 10.1677/jme.1.02082

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We have identified a novel cytosine/thymidine polymorphism of the human steroidogenic acute regulatory (StAR) gene promoter located 3 bp downstream of the steroidogenic factor-1 (SF-1)-binding site and 9 bp upstream of the TATA box (ATTTAAG). Carriers of this mutation have a high prevalence of primary aldosteronism. In transfection experiments, basal StAR promoter activity was unaltered by the mutation in murine Y-1 cells and human H295R cells. In Y-1 cells, forskolin (25 microM, 6 h) significantly increased wild-type promoter activity to 230+/-33% (P<0.05, n=4). In contrast, forskolin increased mutated promoter activity only to 150+/-27%, with a significant 35% reduction compared to wild type (P<0.05, n=3). In H295R cells, angiotensin II (AngII; 10 nM) increased wild-type StAR promoter activity to 265+/-22% (P<0.01, n=3), while mutated StAR promoter activity in response to AngII only reached 180+/-29% of controls (P< 0.01, n=3). Gel mobility shift assays show the formation of two additional complexes with the mutated promoter: one with the transcription repressor DAX-1 and another with a yet unidentified factor, which strongly binds the SF-1 response element. Thus, this novel mutation in the human StAR promoter is critically involved in the regulation of StAR gene expression and is associated with reduced promoter activity, a finding relevant for adrenal steroid response to physiological stimulators.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
UniBE Contributor:	Huynh-Do, Uyen
ISSN:	0952-5041
ISBN:	16901925
Publisher:	Journal of Endocrinology
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:50
Last Modified:	05 Dec 2022 14:15
Publisher DOI:	10.1677/jme.1.02082
PubMed ID:	16901925
Web of Science ID:	000240020600007
URI:	https://boris.unibe.ch/id/eprint/20904 (FactScience: 4700)