Tissue-specific expression of human P-450(AROM). The promoter responsible for expression in adipose tissue is different from that utilized in placenta

Mala S. Mahendroo, Gary D. Means, Carole R. Mendelson, Evan R. Simpson

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

The biosynthesis of estrogens from androgens is catalyzed by a enzyme of the endoplasmic reticulum termined aromatase cytochrome P-450 (P-450(AROM)). The gene encoding P-450(AROM) was isolated in our laboratory utilizing a full-length P-450(AROM) cDNA and a primer-extended cDNA obtained from human placental libraries as probes. We have found that the P-450(AROM) gene spans at least 75 kilobases and the region encoding the P-450(AROM) protein is comprised of nine exons. In addition, there are at least two untranslated exons, I.1 and I.2, upstream of which are found putative promoter sequences thought to be responsible for expression of P-450(AROM) in placenta. To determine if these promoters are utilized to regulate P-450(AROM) expression in adipose tissue, we have used polymerase chain reaction technology in an attempt to amplify the untranslated exons out of human adipose total RNA. The untranslated exons could not be amplified out of adipose RNA although they could be amplified out of placental RNA. When oligonucleotides corresponding to these untranslated exons were used in Northern analysis of RNA from human adipose stromal cells, no hybridizable mRNA species was detectable. Putative promoter sequences 326 and 110 base pairs (bp) upstream of the 5' end of exon II were evaluated as adipose P-450(AROM) promoters by primer extension analysis and S1 nuclease protection assays. Both methods suggest a start site of transcription 26 bp downstream of the TATAAA sequence located 110 bp from the placental intron-exon II junction. These results indicate that tissue-specific regulation of aromatase activity in the human is achieved in part by the use of alternative transcriptional start sites and tissue-specific promoters.

Original languageEnglish (US)
Pages (from-to)11276-11281
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number17
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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