Adrenocorticotropic hormone stimulates CYP11B1 gene transcription through a mechanism involving AP-1 factors

Kuniaki Mukai, Fumiko Mitani, Reiko Agake, Yuzuru Ishimura

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

To elucidate the mechanism(s) by which adrenocorticotropic hormone (corticotropin) stimulates transcription of the steroid 11β-monooxygenase gene (CYP11B1) in adrenocortical cells, the 5'-flanking region of rat CYP11B1 was analyzed using transient transfection and protein-binding assays with mouse adrenocortical Y1 cells. The results indicated that both basal and corticotropin-induced transcriptional activation of CYP11B1 required a common regulatory element containing a binding site for activator protein-1 (AP-1) transcription factors (dimers of the Jun and Fos family proteins) in the 5'-flanking region. Other DNA-binding protein(s) such as transcription factor Ad4BP was not required for either basal or corticotropin-induced transcriptional activation. Corticotropin stimuli were found to induce expression of a subset of the jun and fos family gene products in Y1 cells significantly, while total amounts of AP-1 factors capable of binding to its site in the CYP11B1 promoter did not change greatly. Treatment of rats with corticotropin had similar effects on mRNA levels of the jun and fos family genes in the adrenocortical zona fasciculata cells together with an enhancing effect on the level of CYP11B1 mRNA in the tissue. The effects of corticotropin on mRNA levels of the jun and fos family genes as well as transcription of CYP11B1 in Y1 cells were mimicked by treatment of the cells with dibutyryl cAMP. Furthermore, when components of AP-1 factors were overexpressed by transfecting Y1 cells with their expression vectors, a paired expression of AP-1 components such as c-Jun and c-Fos, which were inducible by corticotropin, transactivated the CYP11B1 promoter more strongly in the absence of corticotropin than other combinations such as JunD and Fra-2 expressed constitutively. These results suggest that corticotropin regulates transcription of the CYP11B1 gene by causing compositional changes in AP-1 transcription factors in the adrenocortical cells via a cAMP-dependent pathway.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalEuropean Journal of Biochemistry
Volume256
Issue number1
Publication statusPublished - 1998 Aug 15

Fingerprint

Steroid 11-beta-Hydroxylase
Transcription Factor AP-1
Transcription
Adrenocorticotropic Hormone
Genes
fos Genes
Transcription Factors
5' Flanking Region
Messenger RNA
Transcriptional Activation
Rats
Steroid Hydroxylases
Chemical activation
Zona Fasciculata
DNA-Binding Proteins
Mixed Function Oxygenases
Protein Binding
Dimers
Transfection
Assays

Keywords

  • Activator protein-1
  • Adrenocorticotropic hormone
  • Cytochrome P-450
  • Glucocorticoid
  • Steroid 11β-hydroxylase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Adrenocorticotropic hormone stimulates CYP11B1 gene transcription through a mechanism involving AP-1 factors. / Mukai, Kuniaki; Mitani, Fumiko; Agake, Reiko; Ishimura, Yuzuru.

In: European Journal of Biochemistry, Vol. 256, No. 1, 15.08.1998, p. 190-200.

Research output: Contribution to journalArticle

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