Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression

Koji Murao, Hitomi Imachi, Wen M. Cao, Xiao Yu, Hiroshi Tokumitsu, Hiroyuki Inuzuka, Norman C.W. Wong, Margaret A. Shupnik, Ryoji Kobayashi, Toshihiko Ishida

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Abstract

TRH binds to a membrane receptor that activates several intracellular signaling pathways and increases transcription of the TSH and prolactin (PRL) genes. Although TRH induces TSH and PRL gene expression, the underlying mechanism is not clear. In this report we examined the role of the Ca 2+/calmodulin-dependent protein (CaM) kinase cascade in mediating TRH-stimulated transcription of TSH and PRL. RT-PCR and Western blot analysis were used to show that CaM kinase kinase (CaM-KK) and CaM IV (CaM-KIV) were present in rat anterior pituitary and its cell line GH3. Next, the effects of constitutively active CaM-KIV (CaM-KIVc) or its dominant negative mutant (CaM-KIVdn) on TSH and PRL promoter activity were tested in GH 3 cells. The results showed that either CaM-KIVc alone or an upstream kinase, CaM-KK, induced the activity of both TSH and PRL promoters. Exposure of GH3 cells to 100 μM TRH induced CaM-KIV activity within 5 min and, as expected, also increased both TSH and PRL promoter activity. In contrast, cells carrying the CaM-KIVdn isoform had suppressed TRH induction of both TSH and PRL promoter activity. These results indicate that the CaM-KK-CaM-KTV cascade probably plays an important role in TRH induction of TSH and PRL transcriptional activity in pituitary cells.

Original languageEnglish
Pages (from-to)4846-4852
Number of pages7
JournalEndocrinology
Volume145
Issue number11
DOIs
Publication statusPublished - Nov 1 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Murao, K., Imachi, H., Cao, W. M., Yu, X., Tokumitsu, H., Inuzuka, H., Wong, N. C. W., Shupnik, M. A., Kobayashi, R., & Ishida, T. (2004). Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression. Endocrinology, 145(11), 4846-4852. https://doi.org/10.1210/en.2004-0544