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Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling
- Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 35(6)
- Publication Year :
- 2021
-
Abstract
- cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
FGF21
medicine.medical_treatment
Transgene
Mice, Transgenic
Growth hormone receptor
Biochemistry
Body Mass Index
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
Genetics
medicine
Animals
IGFBP1
Cyclic AMP Response Element-Binding Protein
Molecular Biology
Transcription factor
Mice, Knockout
Messenger RNA
Chemistry
Growth factor
Binding protein
Gene Expression Regulation, Developmental
Fibroblast Growth Factors
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Liver
Growth Hormone
Body Composition
Female
030217 neurology & neurosurgery
Biotechnology
Signal Transduction
Subjects
Details
- ISSN :
- 15306860
- Volume :
- 35
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES
- Accession number :
- edsair.doi.dedup.....a90f52dccdc6e6d7ae9934dc8dc47c0d