Use of molecular probes to study regulation of aromatase cytochrome P-450

C. R. Mendelson, G. D. Means, M. S. Mahendroo, C. J. Corbin, M. P. Steinkampf, S. Graham-Lorence, E. R. Simpson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Aromatase, an enzyme complex localized in the endoplasmic reticulum of estrogen-producing cells, is composed of NADPH-cytochrome P-450 reductase, and aromatase cytochrome P-450 (cytochrome P-450(AROM)). To define the molecular mechanisms involved in the multifactorial regulation of cytochrome P-450(AROM) in estrogen-producing cells, we have isolated a cDNA specific for human cytochrome P-450(AROM) and have used this cDNA to isolate the human cytochrome P-450(AROM) gene. The cDNA sequence encodes a polypeptide of 503 amino acids and contains - near the carboxy-terminus, a region of high homology with the putative heme-binding regions of other P-450 cytochromes. COS1 cells transfected with an expression plasmid containing the cytochrome P-450(AROM) cDNA had the capacity to aromatize testosterone, androstenedione and 16α-hydroxyandrostenedione, suggesting that a single polypeptide catalyzes all steps of the aromatization reaction using either of the three major C19-substrates. The human cytochrome P-450(AROM) gene is > 52 kb in size and consists of 10 exons and 9 introns. Hormonally induced changes in aromatase activity of human ovarian granulosa and adipose stromal cells are associated with comparable changes in cytochrome P-450(AROM) gene expression and synthesis, whereas the reductase component is only modestly affected. Studies are in progress to define the molecular mechanisms involved in the regulation of cytochrome P-450(AROM) gene expression in estrogen-produced cells.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalBiology of reproduction
Volume42
Issue number1
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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