Characterization of relaxin 3 and its receptors in chicken: Evidence for relaxin 3 acting as a novel pituitary hormone

Abstract

Mammalian relaxin (RLN) family peptides binding their receptors (RXFPs) play a variety of roles in many physiological processes, such as reproduction, stress, appetite regulation, and energy balance. In birds, although two relaxin family peptides (RLN3 and INSL5) and four receptors (RXFP1, RXFP2, RXFP2-like, and RXFP3) were predicated, their sequence features, signal properties, tissue distribution, and physiological functions remain largely unknown. In this study, using chickens as the experimental model, we cloned the cDNA of the cRLN3 gene and two receptor (cRXFP1 and cRXFP3) genes. Using cell-based luciferase reporter assays, we demonstrate that cRLN3 is able to activate both cRXFP1 and cRXFP3 for downstream signaling. cRXFP1, rather than cRXFP3, is a cognate receptor for cRLN3, which is different from the mammals. Tissue distribution analyses reveal that cRLN3 is highly expressed in the pituitary with lower abundance in the hypothalamus and ovary of female chicken, together with the detection that cRLN3 co-localizes with pituitary hormone genes LHB/FSHB/GRP/CART and its expression is tightly regulated by hypothalamic factors (GnRH and CRH) and sex steroid hormone (E2). The present study supports that cRLN3 may function as a novel pituitary hormone involving female reproduction.

Pituitary transcriptome profile from laying period to incubation period of Changshun green-shell laying hens

“…The ligand progesterone, a key steroid hormone produced by granulosa cells, can activate PGR and then together they regulate reproductive cycles [ 40 ]. RLN3 is the most recently identified member of the relaxin peptide family which may be involved in female reproduction in chickens [ 41 ]. It is highly expressed in the pituitary with lower abundance in the hypothalamus, hindbrain, spinal cord and ovary [ 41 ].…”

“…RLN3 is the most recently identified member of the relaxin peptide family which may be involved in female reproduction in chickens [ 41 ]. It is highly expressed in the pituitary with lower abundance in the hypothalamus, hindbrain, spinal cord and ovary [ 41 ]. The expression of RLN3 is tightly regulated by GnRH, corticotropin-releasing hormone and sex steroid hormone (E2) [ 41 ].…”

“…It is highly expressed in the pituitary with lower abundance in the hypothalamus, hindbrain, spinal cord and ovary [ 41 ]. The expression of RLN3 is tightly regulated by GnRH, corticotropin-releasing hormone and sex steroid hormone (E2) [ 41 ]. The relevant literature suggests that RLN3 might be involved in modulating a range of interrelated functions such as responses to stress, memory, circadian rhythm, sleep/wake states, food intake, metabolism, satiety and neuroendocrine function [ 42 – 47 ].…”