Phoenixin
Reproductive / AnxietyAlso known as: PNX-20, PNX-14, Phoenixin-20, Phoenixin-14, SMIM20
Mechanism
Phoenixin is a recently discovered peptide (2013) involved in reproductive function and anxiety. It stimulates GnRH neurons to promote reproductive hormone release and has anxiolytic (anxiety-reducing) effects. It exists as two forms (PNX-14 and PNX-20) and is widely expressed in the hypothalamus, heart, and other tissues. It also appears to play roles in pain modulation, memory, and inflammation.
Technical detail
Phoenixin (PNX) exists as PNX-14 and PNX-20, cleavage products of the SMIM20 gene product. It signals through GPR173 (SREB3), an orphan GPCR enriched in hypothalamic GnRH neurons. PNX-GPR173 activation stimulates GnRH transcription and secretion via cAMP/PKA-CREB signaling. PNX also upregulates kisspeptin receptor (KISS1R) expression on GnRH neurons, amplifying kisspeptin sensitivity. Anxiolytic effects involve modulation of GABAergic signaling in the amygdala and hippocampus. Additional reported effects include anti-inflammatory actions (NF-kB suppression), cardioprotection, and enhancement of memory consolidation.