Research Focus
Cell-cell signalling pathways that underpin ovarian function in health and disease.

Background to the Research
Early progress included identification of the major intra-ovarian feedback loop that helps determine why usually only one follicle ovulates in the human menstrual cycle. The mechanistic insight gained opened the way to safer and more effective treatments using gonadotrophins to stimulate follicular development and ovulation in women receiving fertility treatment. Two international patents have resulted.

Recent Progress
Presently, we study the pro- and anti-inflammatory processes involved in ovulation and possibly the development of ovarian cancer. Most recently, we established that ovulation is a serial injury-repair process in which locally produced glucocorticoids act as natural anti-inflammatory agents. We are currently pursuing evidence that this process is deficient or defective in ovarian cancer.

Proposed model for intracrine amplification of
anti-inflammatory glucocorticoid action by
11ß hydroxysteroid dehydrogenase type1 (11ßHSD1) taken from Hillier SG 2007
JOURNAL OF ENDOCRINOLOGY 195 1-6.
1. Pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFa) bind membrane-associated receptors on target cells to increase the expression of inflammation-associated gene products such as cyclo-oxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). The inflammatory response includes an associated increase in 11ßHSD1 (and/or reduced 11ßHSD2) mRNA and encoded 11-oxoreductase enzymic activity. 2. Cytokine-induced inflammatory mediators bring about haemodynamic, vascular and biochemical changes associated with inflammation. 3. Cortisol (F) formation from cortisone (E) is locally increased due to cytokine enhanced 11-oxoreductase activity. Increased binding of F to glucocorticoid receptor (GR) activates GR-mediated post-receptor anti-inflammatory signalling, leading to resolution of inflammation.

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