Poster Presentation The International Congress of Neuroendocrinology 2014

The role of the novel reproductive peptide phoenixin-20 amide in GnRH and Kiss hypothalamic cell models. (#212)

Alice K Treen 1 , Denise D Belsham 1
  1. University of Toronto, Toronto, ON, Canada

Reproductive function is coordinated by the actions of specific neuropeptides and peripheral hormones, converging on the gonadotropin-releasing hormone (GnRH) neurons of the hypothalamic-pituitary-gonadal (HPG) axis. Phoenixin-20 amide (PNX-20) is a recently described peptide that was found to increase GnRH-stimulated LH secretion and GnRH receptor mRNA at the level of the anterior pituitary (1). To date, no studies have looked at the role of PNX-20 at the level of the hypothalamus, where it is most highly expressed. To elucidate the role of PNX-20 at the level of the hypothalamus, immortalized cell lines representative of GnRH and kisspeptin neurons were studied (2). The mHypoA-GnRH/GFP and mHypoA-Kiss/GFP-3 and -4 cell lines represent populations of GnRH, arcuate nucleus kisspeptin and anteroventral periventricular (AVPV) nucleus kisspeptin neurons, respectively. 10 and 100 nM PNX-20 amide treatment in the mHypoA-GnRH/GFP cell line was found to increase c-fos mRNA expression at 30 minutes and GnRH mRNA expression 2-fold after 2 hours. 1000 nM PNX-20 increased the secretion of GnRH after 1 hour and after a 24-hour pre-treatment. 10 nM PNX-20 increased the phosphorylation of ERK1/2. In both the mHypoA-Kiss/GFP-3 and -4 cell lines, 100 nM PNX-20 increased Kiss-1 mRNA by 2-fold at 24 hours. These experiments are the first to implicate a role for PNX-20 at the level of the hypothalamus. PNX-20 appears to stimulate GnRH transcription, protein synthesis and secretion in GnRH neurons and Kiss-1 transcription in both arcuate and AVPV representative kisspeptin neurons. Although a receptor has not yet been described, PNX-20 may use MAPK signal transduction through ERK1/2 to increase GnRH and kisspeptin synthesis. PNX-20 appears to play an important role at the level of the hypothalamus in the regulation of the HPG axis. This work is generously supported by CIHR and CRC. 

  1. Yosten et al. J Neuroendocrinol. Feb 2013; 25(2): 206–215.
  2. McFadden et al. Mol Cell Endocrinol. 2013 Sep 5;377(1-2):65-74.