prince henry’s institute monash medical centre 246 clayton road, clayton, victoria contacts: dr....

Prince Henry’s InstituteMonash Medical Centre246 Clayton Road, Clayton, Victoria

Contacts:Dr. Morag Young: morag.young@princehenrys.orgProf. Peter Fuller: peter.fuller@princehenrys.org

Steroid Receptor Biology

Mineralocorticoid receptors (MR) and Heart DiseaseMineralocorticoid receptors (MR) and Heart Disease

Heart disease is a leading cause of death in Australia (40%) MR are a key players in this pathology…but how?!

Dr Morag YoungDr Morag Young

Uninephrectomised mouse/rat treated

with aldosterone/DOC plus 0.9% saline

Cardiac FibrosisHypertension Cardiac Hypertrophy

Oxidative Stress

NADPH oxidase

InflammationCOX-2

Osteopontin

Macrophages

8 days

8 weeks

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 DiseaseMineralocorticoid receptors (MR) and Heart DiseaseDr Morag YoungDr Morag Young

Fibrillar collagen

Fibroblast

VSMC

Endothelial cell

Cardiac myocyte

Artery

Macrophage MR-null mice:

No effect on DOC-induced monocyte/macrophage recruitment

Reduced basal gene expression

Cardiac myocyte MR-null mice:

No effect on DOC-induced monocyte/macrophage recruitment

No effect on inflammatory gene expression

Endothelial cell MR-null mice:

Reduced DOC-induced macrophage recruitment at 8 days

MR

MRMR

Granulosa Cell Tumours (GCT)Granulosa Cell Tumours (GCT)Granulosa Cell Tumours (GCT)Granulosa Cell Tumours (GCT)

• 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

Professor Peter FullerProfessor Peter Fuller