The hormonal regulation of the novel reproductive peptide phoenixin in NPY and GnRH hypothalamic models by estrogen, insulin and leptin

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 515-547-Female Reproductive Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-545
Alice K. Treen*1 and Denise D Belsham2
1University of Toronto, Toronto, ON, Canada, 2Univ of Toronto, Toronto, ON, Canada
Phoenixin is a recently described peptide that has been linked to reproductive function. This novel peptide increases GnRH-stimulated LH secretion and up-regulates GnRH receptor mRNA in the anterior pituitary. However, no studies have looked at the regulation of phoenixin at the level of the hypothalamus, where it is most highly expressed, and the central roles it could potentially play in reproduction and energy homeostasis. Phoenixin expression has been detected by qRT- PCR in many of the rodent, immortalized hypothalamic cell lines generated by our laboratory. Initially, the mHypoA-NPY/GFP and mHypo-GnRH/GFP cell lines were selected as models of central neurons from the metabolic and reproductive systems, respectively. We have used the mHypoA-NPY/GFP and mHypo-GnRH/GFP cell lines to help elucidate the regulation of phoenixin by the reproductive hormone estrogen, and the metabolic hormones, insulin and leptin. Both cell lines express estrogen, insulin and leptin receptors. The mHypoA-NPY/GFP cell line was treated with 10 nm of 17-β estradiol and the relative phoenixin mRNA expression was determined by qRT- PCR over a 24-hour time course. Treatment of mHypoA-NPY/GFP hypothalamic cells with 17-β estradiol caused a significant reduction in phoenixin mRNA expression after 1 hour. Preliminary data from the mHypo-GnRH/GFP line indicates that there may also be a direct repressive effect of E2on phoenixin. These results could potentially mimic the direct negative feedback regulation of the reproductive axis by estrogen, and link phoenixin to this process.  Current experiments are underway to investigate the effects of insulin and leptin on phoenixin expression in both cell lines. The molecular pathways involved in phoenixin regulation by these hormones will also be delineated through analysis of both membrane and nuclear receptor activation utilizing specific ER agonists and antagonists. These experiments will help us to understand the role that phoenixin may play in reproduction and energy homeostasis at the level of the hypothalamus and expand our current knowledge of the neuroendocrine axis. These studies may also implicate phoenixin in reproductive or metabolic disorders.

Nothing to Disclose: AKT, DDB

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Sources of Research Support: This research was supported by grants from CIHR, CFI and CRC.