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.

Keywords: electrophysiology; hypothalamus; oxytocin; phoenixin; radioimmunoassay; vasopressin.

Fig. 1.

Vasopressin (AVP) and oxytocin (OT) release from hypothalamo-neurohypophysial explants in response to 100 nM phoenixin-20 amide, expressed as picogram of peptides released per 20-min incubation period (means ± SE; group sizes: n = 9). *P < 0.05 vs. preincubation period, paired Student’s t-test. ***P < 0.001 vs. preincubation.

Fig. 2.

Phoenixin (PNX) depolarizes magnocellular (MNC) paraventricular nucleus (PVN) neurons. A: representative current-clamp recordings from two MNC PVN neurons in slice preparation showing that bath application of 10 nM PNX (horizontal gray bar) caused a depolarization of the membrane potential. Both neurons returned to the baseline membrane potential (dashed line) following washout of PNX. B: range of responses of all MNC PVN neurons (n = 16) elicited by bath application of 10 nM PNX. The horizontal black bars represent the mean change in membrane potential ± SE, while each individual point represents the response of a single MNC neuron. Mean depolarization, 7.1 ± 0.9 mV.

Fig. 3.

Lateral ventricle administration of 3.0 nmol of phoenixin-20 amide, but not saline vehicle, resulted in early gene activation, as mirrored by c-Fos immunoreactivity, in cells of the supraoptic nucleus. A: supraoptic nucleus. A, inset: lack of staining in saline-injected control. B: paraventricular nucleus.

Fig. 4.

Time- and dose-dependent effect of phoenixin-20 amide on plasma vasopressin (AVP; A) and oxytocin (OT; B) levels in conscious male rats. Hormone levels are expressed as picograms of peptide per milliliter plasma (means ± SE; group sizes are indicated within the bars). *P < 0.05, **P < 0.01 vs. 3.0 nmol of phoenixin-20 dose, ANOVA (time and treatment) with Scheffé’s multiple-comparison testing.