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The role of ERĪ² in folliculogenesis
Summary
It is our hypothesis that oestrogen activity via ERβ, limits granulosa cell proliferation by opposing anti-proliferation, anti-apoptic signals such as the NFκβ pathway, and by promoting their differentiation into luteal cells. We seek to identify genes and proteins specifically activated by ERβ.
Description
Oestrogen receptor β (ERβ) is a second oestrogen receptor identified about a decade ago. Its expression is predominantly in prostate in males and in granulosa cells in females. Its role in folliculogenesis and indeed in granulosa cell tumours (GCT) is incompletely understood.
Work from Simon Chu’s PhD thesis suggests that it may be inhibitory to growth and that signalling is repressed in tumourigenesis. This is certainly the case in the cell lines.
In contrast to other nuclear receptors, few if any genes have been identified that are uniquely regulated by ERβ in granulosa cells.
We have a series of strategies in place aimed at understanding the role both in vitro and in vivo of this receptor.
In addition, we have screened for interactions of the receptor with co-regulatory molecules and have a panel of interacting proteins that require full characterisation. This represents novel data that is unique to our laboratory.
A principal aim is to identify genes in granulosa cells that are regulated by ERβ.
These studies use cell culture techniques, expression systems and microarray analysis.
Funding
National Health and Medical Research Council
Ovarian Cancer Research Foundation
Selected Publications
Hussein-Fikret, S., Fuller, P.J. and Gargett C.E. (2005) Expression of steroid receptor coactivators in cultured cells from paired myometrial and fibroid tissues. Journal of the Society for Gynecologic Investigation 12: 445-451.
Hussein-Fikret, S. and Fuller, P.J. (2005) Expression of the nuclear receptor coregulators in ovarian stromal and epithelial tumours. Molecular and Cellular Endocrinology 229: 149-160.
Chu, S. Nishi, Y., Yanase, T., Nawata, H. and Fuller, P.J.(2004) Transrepression of estrogen receptor β signaling by nuclear factor-κB in ovarian granulosa cells. Molecular Endocrinology 18: 1919-1928.
Gargett C.E, Bucak, K., Zaitseva, M., Chu, S., Taylor, N., Fuller, P.J. and Rogers, P.A.W. (2002) Estrogen receptor-α and –β expression in microvascular endothelial cells and smooth muscle cells of myometrium amd leiomyoma. Molecular Human Reproduction 8: 770-775.
Chu, S., Jobling, T., Mamers, P., Burger, H.G. and Fuller, P.J. (2000) Estrogen receptor isoform gene expression in ovarian stromal and epithelial tumors. Journal of Clinical Endocrinology and Metabolism 85: 1200-1205.