Ms Celine Camon1, Dr Jenny Clarkson1, Dr Caroline Decourt1, Professor Katalin Prokai-Tatrai2, Prof Rebecca Campbell1, Dr Mike Garratt1
1Centre for Neuroendocrinology, University Of Otago, Dunedin, New Zealand
2University of North Texas Health Science Center, Fort Worth, USA
Hormone replacement therapy (HRT) is prescribed for menopausal symptoms including hot flushes and weight gain and contains estrogens such as 17-beta-estradiol (17βE2). However, estrogen receptor activation by HRT can increase reproductive cancers and cardiovascular event risk in some patients. As protective metabolic effects of 17βE2 are mediated through the arcuate nucleus of the hypothalamus, restricting 17βE2 actions to the brain could serve as a safer mechanism of HRT.
10β,17B-dihydroxyestra-1,4-dien-3-one (DHED) is a prodrug of 17βE2 which is enzymatically converted to estradiol exclusively within the brain. DHED has demonstrated positive benefit in rodent models of hot flush, cognitive decline and stroke. We hypothesise that DHED treatment in female mice will act within the hypothalamus to provide the same beneficial metabolic effects as 17βE2, while avoiding peripheral actions.
Female mice on a high fat diet (to induce metabolic dysfunction) were split into either control, DHED, or 17βE2 treatment groups. Body weight, uterus weight and glucose tolerance was recorded along with estrogen and progesterone receptor expression in the brain. Findings to date indicate that DHED does not elicit the same protective metabolic effects of 17βE2, suggesting that further drug dosage optimisation is required to assess DHED’s potential to improve metabolic dysfunction.
Biography:
Final year PhD candidate in the Centre For Neuroendocrinology and Department of Anatomy at the University of Otago. Research interests include estrogen delivery in metabolism and ageing, alternative hormone replacement therapy agents in menopause and the neuroendocrine control of metabolic dysfunction.