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J. Biol. Chem., Vol. 268, Issue 26, 19463-19470, 09, 1993
MS Mahendroo, CR Mendelson and ER Simpson
Estrogen biosynthesis is catalyzed by a microsomal enzyme, aromatase
cytochrome P450 (P450arom; the product of the CYP19 gene). The human CYP19
gene comprises nine coding exons, II-X. Additionally, tissue- specific
expression is determined by the use of tissue-specific promoters, which
give rise to P450arom transcripts with unique 5'- noncoding sequences. In
placenta, P450arom transcripts contain one of two 5'-untranslated exons,
I.1 or I.2, while ovarian transcripts instead contain sequence consistent
with the use of a promoter, PII, which is proximal to the start of
translation. To characterize transcripts present in adipose tissue and
adipose stromal cells (ASC) in culture, cDNA libraries were constructed by
the RACE (rapid amplification of cDNA ends) procedure. Four P450arom
transcripts with unique 5' termini were identified, leading to the
characterization of two unique 5'-untranslated exons of the CYP19 gene, I.3
and I.4. Whereas I.3-specific sequence is expressed in adipose tissue as
well as in ACS maintained under all culture conditions, I.4-specific
sequence is apparently present only in breast adipose tissue, and ACS
stimulated with glucocorticoids. On the other hand, PII-specific sequence
is present only in cells stimulated with cAMP analogues and is absent from
cells stimulated with glucocorticoids. We conclude that CYP19 gene
expression in human adipose tissue likely utilizes two novel promoters and,
furthermore, that alternative promoter usage in cultured ASC is a function
of the hormonal environment in which the cells are maintained.
Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235.
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