Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms

Jyoti J. Watters, Daniel Dorsa

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Steroid hormones exert dramatic effects on neuronal expression of genes that encode neuropeptides. Expression of the neurotensin/neuromedin (NT/N) gene in preoptic area neurons is dramatically enhanced by estrogen in vivo, even though its promoter lacks palindromic estrogen response elements. We report here that estrogen promotes transcription of this gene by interactions with the cAMP cascade in a neuronal cell line, SK-N-SH, and in a mouse model. In neuroblastoma cells, estrogen increases cAMP and the phosphorylation of the cAMP response element-binding protein in a time frame that precedes induction of NT/N gene transcription. Interference with the cAMP/protein kinase A signal transduction cascade blocks the ability of estrogen to elicit increases in transcription of this gene. Furthermore, in studies performed in vivo using mice deficient in protein kinase A, estrogen fails to induce increases in NT/N mRNA but retains its ability to promote estrogen response element-dependent progesterone receptor gene transcription. These data represent the first report of a nonclassical effect of estrogen on the expression of an endogenous estrogen-regulated neuropeptide gene through cAMP-mediated mechanisms both in a neuroblastoma cell line and in hypothalamic neurons. More importantly, this 'cross-talk' may represent a more generalized mechanism by which steroid hormones act through other signal transduction cascades to regulate the expression of other genes in the brain.

Original languageEnglish (US)
Pages (from-to)6672-6680
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number17
StatePublished - Sep 1 1998
Externally publishedYes

Fingerprint

Neurotensin
Cyclic AMP-Dependent Protein Kinases
Estrogens
Gene Expression
Genes
Response Elements
Neuropeptides
Neuroblastoma
Signal Transduction
Steroids
Hormones
Neurons
Cell Line
Cyclic AMP Response Element-Binding Protein
Preoptic Area
Progesterone Receptors
Phosphorylation
Messenger RNA

Keywords

  • cAMP
  • Estrogen
  • Gene-transcription
  • Mouse brain
  • Neurotensin
  • Nonclassical
  • Signal transduction
  • SK-N-SH cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms. / Watters, Jyoti J.; Dorsa, Daniel.

In: Journal of Neuroscience, Vol. 18, No. 17, 01.09.1998, p. 6672-6680.

Research output: Contribution to journalArticle

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