Induction of c-fos in pituitary cells by thyrotrophin-releasing hormone and phorbol 12-myristate 13-acetate depends upon Ca2+ influx

S. L. Li, C. Godson, E. Roche, S. J. Zhao, M. Prentki, W. Schlegel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The role of cytosolic free Ca2+ ([Ca2+](i)) in the induction of the immediate early gene c-fos by TRH or by phorbol 12-myristate 13-acetate (PMA) was studied in the clonal pituitary cell line GH4C1. It was found that c-fos mRNA levels were rapidly and transiently increased by TRH at physiological concentrations (1-100nM). The effect of was dependent on a rise in [Ca2+](i), and stimulation of Ca2+ influx was essential for c-fos induction. Cell depolarization with K+, which produces a [Ca2+](i) rise by soliciting Ca2+ influx via voltage-gated Ca2+ channels, was insufficient to induce c-fos. Blockade or downregulation of protein kinase C (PKC) strongly attenuated TRH stimulation of c-fos expression. Direct stimulation of PKC by PMA raised c-fos mRNA levels, but only under conditions permitting Ca2+ influx. We conclude that TRH induces c-fos mRNA by a mechanism dependent on PKC activation and on Ca2+ influx. The essential role of Ca2+ influx for PMA stimulation of c-fos mRNA suggests a novel pathway linking PKC stimulation to early gene expression.

Original languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalJournal of Molecular Endocrinology
Volume13
Issue number3
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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