Starvation‐induced transcription factor CREBH negatively governs body growth by controlling GH signaling

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 2 of 14 | NAKAGAWA et Al.

CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions

“…Similar to FGF21, hepatic CREBH transgenic mice have inhibited growth. CREBH liver-specific transgenic mice exhibit severe GH resistance [71]. Furthermore, Fgf21 transgenic mice have a defect in the GH signaling protein STAT5, but liver-specific CREBH transgenic mice have a deficiency in GH receptor, an upstream molecule of STAT5 [71].…”

“…CREBH liver-specific transgenic mice exhibit severe GH resistance [71]. Furthermore, Fgf21 transgenic mice have a defect in the GH signaling protein STAT5, but liver-specific CREBH transgenic mice have a deficiency in GH receptor, an upstream molecule of STAT5 [71]. Thus, these phenotypes remain when crossing liverspecific CREBH transgenic mice with FGF21 KO mice [71].…”

“…Furthermore, Fgf21 transgenic mice have a defect in the GH signaling protein STAT5, but liver-specific CREBH transgenic mice have a deficiency in GH receptor, an upstream molecule of STAT5 [71]. Thus, these phenotypes remain when crossing liverspecific CREBH transgenic mice with FGF21 KO mice [71]. Liver specific Hrd1 KO, another mouse model with elevated CREBH and FGF21 in the liver, causes the suppression of GH signaling and growth delay [68,69].…”