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Beta-adrenergic control of c-fos expression in fetal and neonatal rat tissues: relationship to cell differentiation and teratogenesis.

Publication ,  Journal Article
Slotkin, TA; Lappi, SE; Seidler, FJ
Published in: Toxicol Appl Pharmacol
August 1995

beta-Adrenergic receptors appear in noradrenergic target tissues well before the arrival of nerve terminals, and are thought to play a role in the control of cell differentiation. We examined the ability of beta-agonists to stimulate expression of the nuclear transcription factor, c-fos, in developing rat liver and heart. This factor has been shown to associated with trophic activation of genes involved in both cell differentiation and cell growth. In response to terbutaline, a beta 2-selective agonist, marked stimulation of c-fos was demonstrated in the liver, which contains beta 2-receptors, on Gestational Day 20, as well as on Postnatal Days 1 and 8. In the heart, which contains predominantly beta 1-receptors, isoproterenol (a non-subtype-selective beta-agonist) was more effective that terbutaline, indicating that either receptor subtype can elicit stimulation of c-fos. In both tissues, the response magnitude increased with age, rather than following changes in receptor number, which increase in the heart but decrease in the liver; the same pattern has been seen for the ability of beta-agonists to promote cell differentiation at the expense of replication; the implication is that ontogenetic changes in post-receptor coupling are much more important than is the number of receptors in determining neurotrophic influences on gene expression and cell development. In keeping with the view that fetal/neonatal beta-adrenergic stimulation of c-fos is related to cell differentiation rather than simply to growth, repeated administration of isoproterenol to neonatal rats did not elicit cardiac hypertrophy, whereas the same treatment did produce hypertrophy in adult rats. The intracellular signaling cascade from beta-receptor to c-fos expression may thus provide one of the basic cellular mechanisms for trophic control of differentiation by biogenic amines, and for the teratologies associated with beta-adrenergic agonist therapy.

Duke Scholars

Published In

Toxicol Appl Pharmacol

DOI

ISSN

0041-008X

Publication Date

August 1995

Volume

133

Issue

2

Start / End Page

188 / 195

Location

United States

Related Subject Headings

  • Toxicology
  • Terbutaline
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • RNA
  • Proto-Oncogene Proteins c-fos
  • Pregnancy
  • Myocardium
 

Citation

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Slotkin, T. A., Lappi, S. E., & Seidler, F. J. (1995). Beta-adrenergic control of c-fos expression in fetal and neonatal rat tissues: relationship to cell differentiation and teratogenesis. Toxicol Appl Pharmacol, 133(2), 188–195. https://doi.org/10.1006/taap.1995.1141
Slotkin, T. A., S. E. Lappi, and F. J. Seidler. “Beta-adrenergic control of c-fos expression in fetal and neonatal rat tissues: relationship to cell differentiation and teratogenesis.Toxicol Appl Pharmacol 133, no. 2 (August 1995): 188–95. https://doi.org/10.1006/taap.1995.1141.
Slotkin, T. A., et al. “Beta-adrenergic control of c-fos expression in fetal and neonatal rat tissues: relationship to cell differentiation and teratogenesis.Toxicol Appl Pharmacol, vol. 133, no. 2, Aug. 1995, pp. 188–95. Pubmed, doi:10.1006/taap.1995.1141.
Journal cover image

Published In

Toxicol Appl Pharmacol

DOI

ISSN

0041-008X

Publication Date

August 1995

Volume

133

Issue

2

Start / End Page

188 / 195

Location

United States

Related Subject Headings

  • Toxicology
  • Terbutaline
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • RNA
  • Proto-Oncogene Proteins c-fos
  • Pregnancy
  • Myocardium