Growth hormone activates X-box binding protein 1 in a sexually dimorphic manner through the extracellular signal-regulated protein kinase and CCAAT/enhancer-binding protein β pathway in rat liver

Nakata, T.; Hirano, Yoshitaka; Katsumata, Harumi; Tokita, Reiko; Yagi, Takashi; Toyoshima, Yuka; Minami, Shiro

doi:10.1507/endocrj.ej19-0240

Cited by 3 publications

(9 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein extraction and western blotting. Isolation of cytoplasmic and nuclear proteins has been described previously [28]. Protein extracts were electrophoresed through SDS polyacrylamide gels.…”

Section: Cell Culture and Transfections (Luciferase)mentioning

confidence: 99%

“…PCR select cDNA subtraction, cloning, and sequencing. Genes induced by GH in HPX rat livers were determined by the SSH technique [6] using the PCR-Select cDNA Subtraction Kit (Clontech Laboratories, Inc., Palo Alto, CA) as described previously [28]. One microgram of total RNA from GH or vehicle-treated rat liver was reverse transcribed using the SMART PCR cDNA Synthesis Kit (Clontech Laboratories, Inc.).…”

Section: Introductionmentioning

confidence: 99%

“…RNA isolation and northern blotting. Total RNA and Poly(A) RNA were isolated as described [28]. 7.5 μg total RNA or 0.5 μg poly(A) RNA was electrophoresed on a 1% agarose and 6% formamide gel, transferred to a Hybond-N+ membrane (GE Healthcare UK Ltd., Buckinghamshire, UK), and hybridized to radiolabeled complementary RNA (cRNA) probes derived from cDNAs as described previously [30].…”

Section: Introductionmentioning

confidence: 99%

“…Real time quantitative RT-PCR (qPCR). cDNA were prepared as described [28]. The oligonucleotides utilized are listed in Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of cells. H4IIE cells expressing the Ghr mRNA (H4IIE GHR) were constructed previously [28], and stored in alpha modified Eagle's medium containing 10% fetal calf serum and 10% DMSO in liquid nitrogen freezer. H4IIE GHR cells at 16-20 passages were used in experiments.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Growth hormone increases regulator of calcineurin 1-4 (Rcan1-4) mRNA through c-JUN in rat liver

et al. 2020

Self Cite

View full text Add to dashboard Cite

Growth hormone (GH) activates multiple signal transduction pathways. To investigate these pathways, we identified novel genes whose transcription was induced by GH in the liver of hypophysectomized (HPX) rats using the suppression subtractive hybridization technique. We found that regulator of calcineurin 1 (Rcan1) mRNA was upregulated by GH administration. RCAN1 regulates the activity of calcineurin, a Ca/calmodulin-dependent phosphatase. Rcan1 encodes two major transcripts, Rcan1-1 and Rcan1-4, resulting from differential promoter use and first exon choice. We found that a single injection of GH increased the levels of Rcan1-4 mRNA and RCAN1-4 protein transiently, but did not increase Rcan1-1 mRNA in HPX rat liver. Then the molecular mechanism of GH to induce Rcan1-4 transcription was examined in rat hepatoma H4IIE cells. Experiments using inhibitors suggested that c-JUN N-terminal kinase was required for the induction of Rcan1-4 mRNA by GH. GH increased the levels of phosphorylated c-JUN protein and c-Jun mRNA in HPX rat liver. The luciferase and electrophoretic mobility shift assays showed that c-JUN upregulated Rcan1-4 mRNA by binding to the cAMP-responsive element in the upstream of Rcan1 exon 4. These results indicate that GH activates c-JUN to affect the activity of calcineurin by the induction of Rcan1-4 in rat liver.

show abstract

Section: Cell Culture and Transfections (Luciferase)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Real time quantitative RT-PCR (qPCR). cDNA were prepared as described [28]. The oligonucleotides utilized are listed in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Growth hormone increases regulator of calcineurin 1-4 (Rcan1-4) mRNA through c-JUN in rat liver

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Obesity Disrupts Pituitary UPR Leading to NAFLD

Qian

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Obesity is the major risk factor for nonalcoholic fatty liver disease (NAFLD), for which effective cures are lacking. Despite the notion that obesity is associated with aberrant levels and action of pituitary hormones that are essential for maintaining hepatic metabolic and inflammatory states, the intrinsic pituitary endocrine abnormalities and their systemic consequences are incompletely defined. By characterizing the impact of diet-induced obesity (DIO) on the pituitary whole tissue and single cell transcriptome, we demonstrated that obesity disrupts pituitary endoplasmic reticulum (ER) homeostasis by suppressing the inositol-requiring enzyme-α (IRE1α)-mediated adaptive unfolded protein response (UPR). We further showed that defective pituitary UPR by IRE1α-deletion in the anterior pituitary strikingly augmented obesity-associated systemic metabolic abnormalities, particularly the NAFLD-associated pathologies. Conversely, enhancing the adaptive UPR in the anterior pituitary, by genetic gain-of-function of spliced X-box binding protein 1 (sXBP1), ameliorated the systemic and hepatic metabolic defects observed in mice with pituitary IRE1α deletion. Intriguingly, disruption of the UPR in the pituitary resulted in impaired hepatic UPR, which was in part due to a defective thyroid hormone receptor (THR)-mediated activation of hepatic Xbp1. In contrast, activation of the hepatic THR signaling improved obesity-associated glucose intolerance and attenuated the impaired hepatic ER homeostasis in anterior pituitary-IRE1α deficient mice. Together, our study provides the first insight into disruption of endocrine signaling-mediated inter-organ UPR communication drives obesity-associated hepatic pathologies. Unraveling these connections might uncover new therapeutic targets for NAFLD and other obesity-associated diseases.

show abstract

ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic

Streeter,

Persaud,

Gao

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionReducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model.MethodsWe generated mice with homozygous floxed Opa1 and Atf4 alleles and a tamoxifen-inducible Cre transgene controlled by the human skeletal actin promoter to enable simultaneous depletion of OPA1 and ATF4 in skeletal muscle (mAO DKO). Mice were fed high fat (HFD) or control diet and evaluated for ISR activation, body mass, fat mass, glucose tolerance, insulin tolerance and circulating concentrations of FGF21 and growth differentiation factor 15 (GDF15).ResultsIn mAO DKO mice, ATF4 induction is absent. Other indices of ISR activation, including XBP1s, ATF6, and CHOP were induced in mAO DKO males, but not in mOPA1 or mAO DKO females. Resistance to diet-induced obesity was not reversed in mAO DKO mice of both sexes. Circulating FGF21 and GDF15 illustrated sexually dimorphic patterns. Loss of OPA1 in skeletal muscle increases circulating FGF21 in mOPA1 males, but not in mOPA1 females. Additional loss of ATF4 decreased circulating FGF21 in mAO DKO male mice, but increased circulating FGF21 in female mAO DKO mice. Conversely, circulating GDF15 was increased in mAO DKO males and mOPA1 females, but not in mAO DKO females.ConclusionSex differences exist in the transcriptional outputs of the ISR following OPA deletion in skeletal muscle. Deletion of ATF4 in male and female OPA1 KO mice does not reverse the resistance to DIO. Induction of circulating FGF21 is ATF4 dependent in males, whereas induction of circulating GDF15 is ATF4 dependent in females. Elevated GDF15 in males and FGF21 in females could reflect activation by other transcriptional outputs of the ISR, that maintain mitokine-dependent metabolic protection in an ATF4-independent manner.

show abstract

Growth hormone activates X-box binding protein 1 in a sexually dimorphic manner through the extracellular signal-regulated protein kinase and CCAAT/enhancer-binding protein β pathway in rat liver

Cited by 3 publications

References 60 publications

Growth hormone increases regulator of calcineurin 1-4 (Rcan1-4) mRNA through c-JUN in rat liver

Growth hormone increases regulator of calcineurin 1-4 (Rcan1-4) mRNA through c-JUN in rat liver

Obesity Disrupts Pituitary UPR Leading to NAFLD

ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic

Contact Info

Product

Resources

About