In:
Journal of Molecular Endocrinology, Bioscientifica, Vol. 37, No. 1 ( 2006-08), p. 71-80
Kurzfassung:
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 μM, 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.
Materialart:
Online-Ressource
ISSN:
0952-5041
,
1479-6813
Sprache:
Unbekannt
Verlag:
Bioscientifica
Publikationsdatum:
2006
ZDB Id:
1478171-2
