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

Autor: Ma Zhiqiang, Xue Qun Chen, Xi Wang, Ji Zeng Du, Qing Liu, Jia Wei Tang, Yang Zhao, Yan Jun Shi, Ping Ping Wang, Coote John
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Transcription
Genetic
Biology
Models
Biological
Receptors
Corticotropin-Releasing Hormone
Biochemistry
Cell Line
Corticotropin-releasing hormone receptor 1
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Endocrinology
Anterior pituitary
Pregnancy
Transcription (biology)
Internal medicine
medicine
Transcriptional regulation
Animals
RNA
Messenger
Promoter Regions
Genetic
Receptor
Molecular Biology
NF-kappa B
Brain
DNA Methylation
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
Cell Hypoxia
Transcription Factor AP-1
030104 developmental biology
medicine.anatomical_structure
Pituitary Gland
Female
Signal transduction
medicine.symptom
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Hormone
Zdroj: Molecular and Cellular Endocrinology. 454:12-22
ISSN: 0303-7207
DOI: 10.1016/j.mce.2017.05.031
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: