The mineralocorticoid receptor is much more than just a regulator of salt and water balance. In addition to the classical target tissues where aldosterone mediates vectorial sodium transport across the epithelia of the distal nephron and distal colon, the MR is found in many other tissues. Dr. Morag Young has extensively characterised the role of the MR in the cardiovascular system and in inflammation using a range of innovative approaches, including transgenic mouse models. The current studies build upon this work together with the work of Dr. Ann Drummond in ovarian granulosa cell biology and recent studies with Dr. Colin Clyne in breast cancer to address the role of the mineralocorticoid receptor in ovarian function and in the breast. This is both a unique and novel series of studies with the potential to create a paradigm shift in our understanding of the biology of breast tissue. Two approaches will be undertaken; an in vivo strategy in which the receptor is specifically deleted from the ovarian granulosa cells or the mammary epithelia by creating tissue-specific MR “knockouts”. In each case the preliminary studies reveal interesting and unexpected phenotypes. Parallel studies in vitro use granulosa and mammary-specific cell lines, induced to express the MR, to identify the molecular events mediated by the MR in these tissues.
Dr Simon Chu, MIMR-PHI Institute, OCRF L’Oreal Paris Research Fellow
Professor Christine Clarke, Westmead Hospital
Professor John Funder, MIMR-PHI Institute
Associate Professor Tim Cole, Biochemistry, Monash University
Dr Jane Visvader, Walter & Eliza Hall Institute
Muscat, G., Eriksson, N., Byth, K., Loi, S., Graham D., Jindal, S., Davis, M., Clyne, C. Funder, J.W., Simpson, E.R., Ragan, M., Kuczek, E., Fuller, P.J., Tilley, W., Leedman, P. and Clarke, C. Nuclear receptors transcriptome: discriminant and prognostic value in breast cancer. Molecular Endocrinology, 27:350-356, 2013.
Rickard, A.J., Morgan, J., Tesch, G., Funder, J.W., Fuller, P.J. and Young, M.J. Deletion of mineralocorticoid receptors from macrophages protects against DOC/salt-induced cardiac fibrosis and increased blood pressure. Hypertension 54: 537-43, 2009.
Cato, A.C. and Fuller, P.J.What is in a name? Molecular and Cellular Endocrinology 350: 145, 2012.