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Steroid Receptor Biology
Prince Henry’s Institute
Monash Medical Centre
246 Clayton Road, Clayton, Victoria
Contacts:
Dr. Morag Young: [email protected]
Prof. Peter Fuller: [email protected]
Mineralocorticoid receptors (MR) and Heart Disease
Dr Morag Young
Heart disease is a leading cause of death in Australia (40%)
MR are a key players in this pathology…but how?!
Uninephrectomised
mouse/rat treated
with aldosterone/DOC
plus 0.9% saline
8 days
Oxidative Stress
NADPH oxidase
Macrophages
Inflammation
COX-2
Osteopontin
8 weeks
Hypertension
Cardiac Fibrosis
Cardiac Hypertrophy
We have 3 tissue selective MR knockout mouse strains that we
are using to determine the specific role of the MR in heart
Mineralocorticoid receptors (MR) and Heart Disease
Dr Morag Young
Endothelial cell MR-null mice:
Reduced DOC-induced macrophage
recruitment at 8 days
Fibrillar
collagen
Endothelial
cell
Fibroblast
MR
Artery
Cardiac
myocyte
VSMC
MR
MR
Macrophage MR-null mice:
Cardiac myocyte MR-null mice:
No effect on DOC-induced
monocyte/macrophage recruitment
No effect on inflammatory gene
expression
No effect on DOC-induced
monocyte/macrophage
recruitment
Reduced basal gene expression
Granulosa Cell Tumours (GCT)
Professor Peter Fuller
• Comprise 5% of malignant ovarian tumours
• Molecular analysis of tumour bank and cell lines
•Tissue selective knockout of IKK signalling in ovaries
Our focus has been on:
• profiles of gene expression: candidates & microarray
• signalling pathways – constitutive activation
• expression of ER
•coregulatory molecules
• ERβ-induced genes
• mutation detection
•Implications for normal granulosa cells