SFEBES2021 Poster Presentations Reproductive Endocrinology (31 abstracts)
The effect of exogenous kisspeptin administration in a novel mouse model of hypothalamic amenorrhoea
Jed V Shrewsbury 1 , Kah-Yan Ng 1 , Caitlin McIntyre 2 , Xiao Feng Li 3 , Maria Phylactou 1 , Kevin T O’Byrne 2 , Ali Abbara 1 , Waljit S Dhillo 1 & Bryn M Owen 1
1Section of Endocrinology and Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; 2King’s College London, London, United Kingdom; 3Imperial College London, London, United Kingdom
Kisspeptin is integral to hypothalamo-pituitary-gonadal (HPG) axis function and overall fertility. Functional deficiency of GnRH/lH secretion in the central reproductive disease, hypothalamic amenorrhoea (HA), indicates diminished kisspeptin signalling. Clinical trials have shown kisspeptin to be a viable therapeutic intervention. However, repeated administration led to the development of tachyphylaxis and so is likely a problem for future implementation. Indeed, elevated LH responsiveness suggests increased Kiss1R expression, increasing the pathway’s susceptibility to desensitisation through heightened sensitivity. Together suggesting that improved understanding of the Kiss1-Kiss1R system in HA is necessary to devise an effective long-term treatment strategy. Thus, we aimed to create a novel model of HA in mice, based on body weight reduction induced by chronic caloric restriction, and conduct preliminary investigations into kisspeptin responsiveness and gene expression. Following 60% caloric restriction, mice displayed acyclicity and reduced body weight and fat mass. Upon kisspeptin stimulation, LH responses were elevated. Concomitantly, Kiss1R expression was upregulated. These data replicate the human HA phenotype in a mouse models, displaying increased LH responsiveness in mice following chronic calorie restriction. This model has the potential to inform future therapeutic regimens, possibly with dose titrating, to restore HPG axis function and fertility in women with HA.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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