The integration of multiple signaling pathways provides for bidirectional control of CRHR1 gene transcription in rat pituitary cell during hypoxia

Research output: Contribution to journalArticlepeer-review


  • Yan Jun Shi
  • Zhi Qiang Ma
  • Jia Wei Tang
  • Yang Zhao
  • Xi Wang
  • Qing Liu
  • Ping Ping Wang
  • Xue Qun Chen
  • Ji Zeng Du

Colleges, School and Institutes

External organisations

  • Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Zhejiang University
  • WHO Collaborating Center for Research in Human Reproduction, Division of Science and Technology & Foreign Affairs, National Research Institute for Family Planning


Hypoxia upregulates hypothalamic corticotrophin releasing hormone (CRH) and its receptor type-1 (CRHR1) expression and activates the HPA axis and induces hypoxic sickness and behavioral change. The transcriptional mechanism by which hypoxia differently regulates CRHR1 expression remains unclear. Here we report hypoxia time-dependently induced biphasic expression of CRHR1mRNA in rat pituitary during different physiological status. Short exposure of gestational dams to hypoxia reduced CRHR1mRNA in the pituitary of P1-P14 male rat offspring. A short- and prolonged-hypoxia evoked biphasic response of CRHR1mRNA characterized initially by decreases and subsequently by persistent increases, mediated by a rapid negative feedback via CRHR1 signaling and positive transcriptional control via NF-κB, respectively. Further analysis of CRHR1 promoter in cultured primary anterior pituitary and AtT20 cells showed that c-Jun/AP-1 delivered negative while HIF-1α and NF-κB delivered positive control of transcription at CRHR1 promoter. The negative and positive inputs are integrated by hypoxic initiation and duration in CRHR1 transcription.


Original languageEnglish
JournalMolecular and Cellular Endocrinology
Early online date29 May 2017
Publication statusE-pub ahead of print - 29 May 2017


  • AP-1 , CRH , Corticotrophin-releasing hormone receptor 1 , Hypoxia , NF-κB , Transcription