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Mineralocorticoid receptor regulation of gene expression
Summary
The mineralocorticoid receptor (MR) principally acts by regulating the expression of its target genes. We have identified a number of genes that regulate the MR and are seeking to understand the mechanisms of that regulation in vitro and in vivo.
Description
The adrenal steroid aldosterone is a key regulator of blood pressure. Excessive aldosterone levels cause hypertension and contribute to the pathogenesis of cardiac disease. Our laboratory has a program focused on various aspects of aldosterone action and regulation of gene expression.
This project examines the mechanisms by which the receptor protein for aldosterone, the MR, acts as a transcription factor to regulate gene expression.
The group has over several years identified a series of genes that are regulated by aldosterone. There has been very little work to characterise the interaction of the MR with the DNA and in particular with specific regulatory regions in the DNA.
This project consists of two components.
Firstly, the identification of novel aldosterone-regulated genes, including examining tissues not normally thought of as aldosterone target tissues
Secondly, we are taking specific genes and analysing the regulatory regions to identify the point at which the MR interacts with the promoter region of the gene.
Funding
National Health and Medical Research Council
Selected Publications
Wong, S., Brennan, F.E., Young, M.J., Fuller, P.J. AND Cole, T.J. (2007) A direct effect of aldosterone on endothelin-1 gene expression in vivo. Endocrinology 148:1511-7.
Brennan, F.E. and Fuller, P.J. (2006) Mammalian K-ras2 is a corticosteroid-induced gene in vivo. Endocrinology 147: 2809-2816.
Fuller, P.J. Young, M. J. (2005) Mechanisms of mineralocorticoid action. Hypertension 46: 1227-1235.
Fuller, P.J., Brennan, F.E. and Burgess, J.S. (2000) Acute differential regulation by corticosteroids of epithelial sodium channel subunit and Nedd4 mRNA levels in the distal colon. Pflügers Archives - European Journal of Physiology 441: 94 -101.
Brennan, F.E. and Fuller, P.J. (2000) Rapid upregulation of serum and glucocorticoid-regulated kinase (sgk) gene expression by corticosteroids in vivo. Molecular and Cellular Endocrinology 166: 129-136.
Rogerson, F.M. and Fuller, P.J. (2000) Mineralocorticoid action. Steroids 65: 61-73.
Brennan, F.E. and Fuller, P.J. (1999) Acute regulation by corticosteroids of channel-inducing factor gene messenger ribonucleic acid in the distal colon. Endocrinology 140: 1213-1218.
Brennan, F.E. and Fuller, P.J. (1999) Transcriptional control by corticosteroids of CHIF gene expression in the rat distal colon. Clinical and Experimental Physiology and Pharmacology 26: 489 - 491.