On the steroid requirement for induction of tyrosine aminotransferase by N6, O2-dibutyryl cyclic AMP in hepatoma cells

James L. Hargrove, Gary Volentine, Daryl K. Granner

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Dibutyryl cyclic AMP induces tyrosine aminotransferase significantly in several lines of cultured cells derived from either normal rat liver or hepatomas even when glucocorticoids are not present in the culture medium. Preincubation of the cells with glucocorticoids, however, markedly augments the subsequent response to the cyclic nucleotide. The ability of different classes of steroids to promote induction of tyrosine aminotransferase by dibutyryl cyclic AMP was defined by incubation with glucocorticoid agonists and antagonists prior to the addition of dibutyryl cyclic AMP. Steroids with glucocorticoid activity enhance the induction of tyrosine aminotransferase by dibutyryl cyclic AMP, and yield an increased level of immunoreactive enzyme in the cells. Inactive steroids and glucocorticoid antagonists are ineffective in this regard. Thus, dexamethasone (an optimal agonist) and 21-deoxycortisol (a partial agonist) promote enzyme induction by dibutyryl cyclic AMP. Progesterone, testosterone and 17β-estradiol (glucocorticoid antagonists) and tetrahydrocortisol (an inactive agent) neither induce the enzyme themselves nor amplify the induction by dibutyryl cyclic AMP. Progesterone and other antagonists, however, inhibit the induction of tyrosine aminotransferase by dexamethasone alone or combined with dibutyryl cyclic AMP in both HTC and H-35 monolayer cultures. Glucocorticoids and cyclic AMP therefore act independently to induce tyrosine aminotransferase in the basal state, but also interact to produce a response that is much more than additive and requires the steroid receptor.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalJournal of Steroid Biochemistry
Volume14
Issue number1
DOIs
StatePublished - Jan 1981

Keywords

  • 11β-hydroxyprogesterone, 11β-hydroxy-4-pregnene-3,20-dione
  • 17β-estradiol, estra-1,3,5(10)-triene-3,17β-diol
  • and tetra-hydrocorticosterone, 3α,11β,21-trihydroxy-5β-pregnane-30-one
  • androstenedione, 17-keto-4-androstene-3-one
  • cortisol, 11β,17α,21-trihydroxy-4-pregnene-3,20-dione
  • deoxycorticosterone, 21-hydroxy-4-pregnene-3,20-dione
  • dexamethasone, 9α-fluoro-16α-methyl-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione
  • progesterone, 4-pregnene-3,20-dione
  • testosterone, 17β-hydroxy-4-androstene-3-one

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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