Liganded and unliganded steroid receptor modulation of beta 1 adrenergic receptor gene transcription.

Abstract:

:The classical model of gene regulation by hormones involves a hormone-bound receptor interacting with a DNA response element to increase or decrease gene transcription. Steroid hormone regulation more commonly involves atypical cis-elements, co-receptors, accessory proteins, and unique modes of interaction on different genes. The thyroid hormone and retinoic acid receptors belong to the super family of steroid nuclear receptors and may modify gene expression even in the absence of ligand binding. In these studies, we characterized thyroid receptor- and retinoic acid receptor-mediated regulation of beta1 adrenergic receptor (beta1AR) gene expression. Using cloned fragments of the ovine beta1AR in a luciferase reporter vector, we examined the effects of thyroid receptor and retinoic acid receptor, alone and in combination with T3 or retinoic acid on beta1AR expression. We examined expression in SK-N-SH neuroblastoma cells, CV-1 fibroblasts, and, in neonatal rat, primary cardiomyocytes. We demonstrated that even in the absence of ligand binding, thyroid receptor and retinoic acid receptor can significantly increase beta1AR transcription activity. This effect is important in the developmental transition in beta1AR expression during fetal and postnatal life.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

McNab TC,Tseng YT,Stabila JP,McGonnigal BG,Padbury JF

doi

10.1203/00006450-200111000-00007

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

575-80

issue

5

eissn

0031-3998

issn

1530-0447

journal_volume

50

pub_type

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