TY - JOUR
T1 - Tissue-specific promoters regulate aromatase cytochrome P450 expression
AU - Simpson, Evan R.
AU - Mahendroo, Mala S.
AU - Means, Gary D.
AU - Kilgore, Michael W.
AU - Jo Corbin, C.
AU - Mendelson, Carole R.
PY - 1993
Y1 - 1993
N2 - In humans, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory indicates that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus, the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start site. This promoter is not utilized in placenta; instead, the promoter used to drive aromatase expression in placenta is ≥40 kb upstream from the translational start site. In addition, a minor promoter used in the expression of a small proportion of placental transcripts is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues, including placenta-related cells such as JEG-3 choriocarcinoma cells and hydatidiform moles and other fetal tissues such as fetal liver. In adipose tissue, on the other hand, expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5′-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.
AB - In humans, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory indicates that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus, the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start site. This promoter is not utilized in placenta; instead, the promoter used to drive aromatase expression in placenta is ≥40 kb upstream from the translational start site. In addition, a minor promoter used in the expression of a small proportion of placental transcripts is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues, including placenta-related cells such as JEG-3 choriocarcinoma cells and hydatidiform moles and other fetal tissues such as fetal liver. In adipose tissue, on the other hand, expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5′-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.
KW - Adipose tissue
KW - Brain
KW - Estrogen biosynthesis
KW - Genes
KW - Ovary
KW - Placenta
UR - http://www.scopus.com/inward/record.url?scp=0027405313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027405313&partnerID=8YFLogxK
M3 - Article
C2 - 8432022
AN - SCOPUS:0027405313
SN - 0009-9147
VL - 39
SP - 317
EP - 324
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 2
ER -