The PKC and ERK/MAPK pathways regulate glucocorticoid action on TRH transcription.

Neurochemical Research
Antonieta Cote-VélezP Joseph-Bravo

Abstract

Biosynthesis of TRH, a neuropeptide involved in energy homeostasis, is modulated by glucocorticoids. TRH mRNA and peptide levels are increased upon incubation of hypothalamic cells with dexamethasone or with cAMP analogs but when combined, a mutual antagonism is observed. These effects are observed at the transcriptional level and on binding of glucocorticoid receptor (GR) or pCREB to the composite GRE (cGRE) and CRE-2 sites of TRH promoter. The present work studied the involvement of PKC and MAPK pathways on the effect of dexamethasone and on its interaction with cAMP signaling in hypothalamic cell cultures. PKC or MEK inhibition abolished dexamethasone-stimulatory effect on TRH mRNA levels, as well as its interference with the stimulatory effect of 8Br-cAMP. Binding of nuclear extracts from hypothalamic or neuroblastoma cells stimulated with dexamethasone or 8Br-cAMP to oligonucleotides containing the CRE or cGRE sites of TRH gene promoter was decreased if cells were preincubated with PKC or MEK inhibitors. Mutations on the AP-1 or the GRE half sites of cGRE showed that GR binds as an heterodimer on cGRE, and PKC or MEK inhibitors diminish binding at the AP-1 site. PKC and ERK signaling thus modulate GR activity and its inter...Continue Reading

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Citations

Dec 1, 2012·Molecular Pharmacology·Qin Wang, John R Traynor
Mar 25, 2017·Molecular Medicine Reports·Nae TakizawaHisao Yamada
Apr 16, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·T XiaF Guo
Jan 8, 2015·The Journal of Endocrinology·Patricia Joseph-BravoJean-Louis Charli
Jul 28, 2011·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Stéphanie Decherf, Barbara A Demeneix
Aug 16, 2016·Reviews in Endocrine & Metabolic Disorders·Patricia Joseph-BravoJean-Louis Charli
Sep 22, 2009·Brain Research·Alfonso Carreón-RodríguezLeonor Pérez-Martínez
Jan 27, 2011·Biochimica Et Biophysica Acta·Antonieta Cote-VélezPatricia Joseph-Bravo

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