Major Role of 3′,5′-Cyclic Adenosine Monophosphate-Dependent Protein Kinase A Pathway in Corticotropin-Releasing Factor Gene Expression in the Rat Hypothalamus in Vivo

Keiichi Itoi, Nobuo Horiba, Fumiko Tozawa, Yoko Sakai, Ken Sakai, Keishi Abe, Hiroshi Demura, Toshihiro Suda

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

To assess whether the cAMP-dependent protein kinase-A and/or the diacylglycerol-dependent protein kinase C (PKC) pathways play important roles in the activation of CRF neurons in vivo under physiological conditions, we tested the effect of microinjection of 8-bromo-cAMP (8-Br-cAMP) or 12-O-tetradecanoyl phorbol 13-acetate (TPA) into both paraventricular nuclei (PVN) of the hypothalamus in conscious rats. Both 8-Br-cAMP and TPA increased plasma ACTH concentrations and the POMC messenger RNA (mRNA) concentrations in the anterior pituitary. While injection of 8-Br-cAMP also increased CRF mRNA concentrations in hypothalamic tissue containing the PVN, TPA injection had no effect on CRF mRNA concentrations there. During insulin-induced hypoglycemia, which stimulates CRF gene expression and release, c-fos and c-jun mRNA increases in the hypothalamic tissue preceded the increase in the CRF mRNA level after insulin-induced hypoglycemia. Antisense oligodeoxyribonucleotides (oligos) directed against c-fos, c-jun, or the cAMP response element binding protein (CREB) mRNA were injected into both PVN before insulin-induced hypoglycemia to assess whether activator protein-1 or CREB mediates transcriptional activation of CRF during hypoglycemia. Only antisense oligo against CREB mRNA reduced the CRF mRNA level after insulin-induced hypoglycemia. These results suggest that protein kinase A may transduce intracellular signals in CRF neurons under physiological conditions and raises the possibility that CREB may be involved in stress-induced CRF gene expression.

Original languageEnglish
Pages (from-to)2389-2396
Number of pages8
JournalEndocrinology
Volume137
Issue number6
DOIs
Publication statusPublished - 1996 Jan 1

ASJC Scopus subject areas

  • Endocrinology

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