Novel regulator of vasopressin secretion: phoenixin

Abstract

The newly described hypothalamic peptide, phoenixin, is produced in the hypothalamus and adenohypophysis, where it acts to control reproductive hormone secretion. Both phoenixin and its receptor GPR173 are expressed in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, suggesting additional, nonreproductive effects of the peptide to control vasopressin (AVP) or oxytocin (OT) secretion. Hypothalamo-neurohypophysial explants released AVP but not OT in response to phoenixin. Intracerebroventricular administration of phoenixin into conscious, unrestrained male and female rats significantly increased circulating AVP, but not OT, levels in plasma, and it increased immediate early gene expression in the supraoptic nuclei of male rats. Bath application of phoenixin in hypothalamic slice preparations resulted in depolarization of PVN neurons, indicating a direct, neural action of phoenixin in the hypothalamus. Our results suggest that the newly described, hypothalamic peptide phoenixin, in addition to its effects on hypothalamic and pituitary mechanisms controlling reproduction, may contribute to the physiological mechanisms regulating fluid and electrolyte homeostasis.

Phoenixin and Its Role in Reproductive Hormone Release

“…To investigate this further, Phoenix Pharmaceuticals devised antibodies to the predicted peptide that were used to identify the endogenous peptide for purification. 3 This work identified two predominant isoforms-N-terminally truncated 14 amino acid form identified in cardiac tissue and a 20 amino acid peptide identified in the brain. It has now been demonstrated that phoenixin is cleaved from the C-terminal of small integral membrane protein 20 (SMIM20), although it is yet to be determined how it is cleaved-either by a prohormone convertase or alternatively by ectodomain shedding.…”

Phoenixin—A Pleiotropic Gut-Brain Peptide

“…Most of the functions of phoenixin including potentiation of gonadotropin-releasing hormone (GnRH)-dependent secretion of LH, augmentation of mRNA (messenger ribonucleic acid) expression in GnRH and kisspeptin neurons, stimulation or suppression of reproductive genes, e.g., C/EBP (CCAAT/enhancer-binding protein) mRNA [ 23 ], delaying the onset of estrus [ 24 ] and the increase of plasma vasopressin levels [ 25 ] were shown to be mediated through the GRP173 (G protein-coupled receptor 173). Conversely, blockade of the receptor using GPR173 siRNA (silencing RNA) abolished these effects [ 23 , 24 , 25 ].…”

“…Since phoenixin was also detected in the SON [ 11 ], phoenixin-20’s effect on vasopressin and oxytocin expression was examined. Icv injection of phoenixin-20 resulted in an increase of circulating vasopressin levels 20–30 min after injection [ 25 ]. Blockade of the GPR173 using GPR173 siRNA administered into the brain ventricle for two consecutive days completely abolished this effect [ 25 ].…”

“…Icv injection of phoenixin-20 resulted in an increase of circulating vasopressin levels 20–30 min after injection [ 25 ]. Blockade of the GPR173 using GPR173 siRNA administered into the brain ventricle for two consecutive days completely abolished this effect [ 25 ]. In vitro, phoenixin-20 depolarized magnocellular neurons followed by augmented action potential frequency leading to stimulation of vasopressin hormone expression in hypothalamic explants as well as to gene activation in the SON.…”

“…In vitro, phoenixin-20 depolarized magnocellular neurons followed by augmented action potential frequency leading to stimulation of vasopressin hormone expression in hypothalamic explants as well as to gene activation in the SON. In contrast, no alterations in oxytocin protein expression in vitro, or plasma levels in vivo were induced by phoenixin-20 [ 25 ]. It remains to be investigated whether these alterations in vasopressin levels have effects on fluid homeostasis and/or vascular parameters.…”