A Novel Reproductive Peptide, Phoenixin

Abstract

Normal anterior pituitary function is essential for fertility. Release from the gland of the reproductive hormones LH and FSH is regulated primarily by hypothalamically-derived gonadotropin releasing hormone (GnRH), although other releasing factors have been postulated to exist. Using a bioinformatic approach, we have identified a novel peptide, phoenixin, that regulates pituitary gonadotropin secretion by modulating expression of the GnRH receptor, an action with physiologically relevant consequences. Compromise of phoenixin in vivo using siRNA resulted in the delayed appearance of oestrus and a reduction in GnRH receptor expression in the pituitary. Phoenixin may represent a new class of hypothalamically-derived pituitary priming factors (PFs) that sensitise the pituitary to the action of other RFs, rather than directly stimulating the fusion of secretory vesicles to pituitary membranes.

The novel neuropeptide phoenixin is highly co-expressed with nesfatin-1 in the rat hypothalamus, an immunohistochemical study

“…Present immunofluorescent studies confirm the main pattern of PNX distribution in the rat brain [20], but the structural analysis to date has been strictly focused on hypothalamic regions. Thus, the supraoptic and paraventricular nuclei, perifornical area and zona incerta seem to be basic centres of intense PNX immunoreactivity in the rat brain.…”

“…Populations of PNX positive cells were found in the rat hypothalamus, spinal trigeminal and solitary tracts, spinal cord [20] and even in the trigeminal and nodose ganglia [21]. This newly described endogenous regulator has the potential to control reproductive hormone secretion via modulation of the receptor for the pituitary gonadotropin-releasing hormone (GnRH).…”

“…This newly described endogenous regulator has the potential to control reproductive hormone secretion via modulation of the receptor for the pituitary gonadotropin-releasing hormone (GnRH). Moreover, PNX may sensitize the pituitary to releasing factors, rather than directly promote exocytosis of secretory vesicles from endocrine cells [20].…”

“…Evidence also indicates that PNX may play a significant role in mediating reproduction at the level of the hypothalamic centres [20] and when exogenously administered may preferentially suppress visceral as opposed to thermal pain [21].…”

Nesfatin-1: functions and physiology of a novel regulatory peptide

“…Furthermore, the recently discovered neuropeptide phoenixin, which is colocalized with NUCB2/nesfatin-1 in a number of hypothalamic nuclei (ARC, PVN, ventromedial and lateral hypothalamus) has been suggested as a potential mediator for nesfatin-1's action with regard to reproduction. Phoenixin increases GnRH, GnRH receptor and Kiss1 gene expression (Yosten et al 2013, Treen et al 2016 and potentiates GnRH-stimulated LH release in vitro (Yosten et al 2013). These findings were substantiated by an in vivo study demonstrating that i.c.v.…”