Aromatase P450 gene expression in human adipose tissue: Role of a Jak/STAT pathway in regulation of the adipose-specific promoter

Ying Zhao, John E. Nichols, Serdar E. Bulun, Carole R. Mendelson, Evan R. Simpson

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Abstract

In the present report we describe a heretofore unrecognized role for a Jak/STAT signaling pathway, namely the stimulation of expression of the aromatase P450 (CYP19) gene, and hence of estrogen biosynthesis, in human adipose tissue. Expression of this gene in adipose tissue as well as in adipose stromal cells maintained in the presence of serum and glucocorticoids is regulated by a distal TATA-less promoter, I.4, which contains a glucocorticoid response element, an Sp1 binding site, and an interferon-γ activation site (GAS) element. The stimulatory action of serum (in the presence of dexamethasone) can be replaced by interleukin (IL)-11, leukemia inhibitory factor, and oncostatin-M, as well as by EL-6, providing the IL-6 soluble receptor is also present. Stimulation of the cells by these factors led to rapid phosphorylation of Jak1, but not Jak2 or Jak3, on tyrosine residues. STAT3 but not STAT1 was also phosphorylated and bound to the GAS element in the 1.4 promoter region. When regions of this promoter were fused upstream of the chloramphenicol acetyltransferase reporter gene and transfected into the cells, mutagenesis or deletion of the GAS element led to complete loss of reporter gene expression. Since adipose tissue is the major site of estrogen biosynthesis in men and in postmenopausal women, this pathway involving a Jak/STAT signaling mechanism acting together with glucocorticoids and Sp1 appears to be the principal means whereby estrogen biosynthesis is regulated in the elderly.

Original languageEnglish (US)
Pages (from-to)16449-16457
Number of pages9
JournalJournal of Biological Chemistry
Volume270
Issue number27
StatePublished - Jul 7 1995

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Aromatase
Biosynthesis
Gene expression
Glucocorticoids
Adipose Tissue
Estrogens
Genes
Tissue
Reporter Genes
Gene Expression
Genetic Promoter Regions
Oncostatin M
Interleukin-11
Leukemia Inhibitory Factor
Interleukin-6 Receptors
Mutagenesis
Phosphorylation
Chloramphenicol O-Acetyltransferase
Response Elements
Stromal Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Aromatase P450 gene expression in human adipose tissue : Role of a Jak/STAT pathway in regulation of the adipose-specific promoter. / Zhao, Ying; Nichols, John E.; Bulun, Serdar E.; Mendelson, Carole R.; Simpson, Evan R.

In: Journal of Biological Chemistry, Vol. 270, No. 27, 07.07.1995, p. 16449-16457.

Research output: Contribution to journalArticle

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