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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00595

Identification of A Novel Functional Corticotropin-releasing Hormone (CRH2) in Chickens and Its roles in Stimulating Pituitary TSHβ Expression and ACTH secretion

 Guixian Bu1, Jie Fan1,  Ming Yang1, Can Lv2, Yin Lin3, Jinxuan Li1, Fengyan Meng1, Xiaogang Du1, Xianyin Zeng1*,  Jiannan Zhang2, Juan Li2 and  Yajun Wang2*
  • 1Sichuan Agricultural University, China
  • 2Sichuan University, China
  • 3College of Life Science, Sichuan Agricultural University, China

Corticotropin-releasing hormone (CRH), together with its structurally and functionally related neuropeptides, constitute the CRH family and play critical roles in multiple physiological processes. Recently, a novel member of this family, namely CRH2, was identified in vertebrates, however, its functionality and physiological roles remains an open question. In this study, using chicken (c-) as the animal model, we characterized the expression and functionality of CRH2 and investigated its roles in anterior pituitary. Our results showed that (1) cCRH2 cDNA is predicted to encode a 40-aa mature peptide, which shares a higher amino acid sequence identity to cCRH (63%) than to other CRH family peptides (23-38%); (2) Using pGL3-CRE-luciferase reporter system, we demonstrated that cCRH2 is ~15 fold more potent in activating cCRH receptor 2 (CRHR2) than cCRHR1 when expressed in CHO cells, indicating that cCRH2 is bioactive and its action is mainly mediated by CRHR2; (3) Quantitative real-time PCR revealed that cCRH2 is widely expressed in chicken tissues including the hypothalamus and anterior pituitary, and its transcription is likely controlled by promoters near exon 1, which display strong promoter activity in cultured DF-1 and HEK293 cells; (4) In cultured chick pituitary cells, cCRH2 potently stimulates TSHβ expression and shows a lower potency in inducing ACTH secretion, indicating that pituitary/hypothalamic CRH2 can regulate pituitary functions. Collectively, our data provides the first piece of evidence to suggest that CRH2 play roles similar, but non-identical, to those of CRH, such as its differential actions on pituitary, and this helps to elucidate the roles of CRH2 in vertebrates.

Keywords: CRH receptor, ACTH and TSH, Pituitary, CRH2, chicken

Received: 30 May 2019; Accepted: 13 Aug 2019.

Copyright: © 2019 Bu, Fan, Yang, Lv, Lin, Li, Meng, Du, Zeng, Zhang, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Xianyin Zeng, Sichuan Agricultural University, Ya'an, 625014, Sichuan, China,
Prof. Yajun Wang, Sichuan University, Chengdu, 610065, Sichuan Province, China,