Expression of enzymes involved in synthesis and metabolism of estradiol in human breast as studied by immunocytochemistry and in situ hybridization.
It is well documented that human breast is actively involved in the local formation of estrogens. To determine the site(s) of action of enzymes involved in synthesis and metabolism of the most potent estrogen estradiol (E2), we have studied the expression of the following enzymes: 3beta-hydroxysteroid dehydrogenase (3-HSD), 17beta-HSD types 1, 2, 5, 7 and 12, aromatase, steroid sulfatase (STS) and estrogen sulfotransferase (EST) 1E1 at the cellular level in breast. Both in situ hybridization and immunocytochemistry were used for enzyme localization in normal breast tissues. For immunocytochemistry, we used rabbit antibodies, while in situ hybridization studies were performed using (35S)-labeled cRNA probes. Similar results were obtained with both approaches. All the enzymes (3beta-HSD; 17beta-HSD types 1, 5, 7 and 12; aromatase) involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2 as well as STS which converts estradiol sulfate (E2-S) to E2 have been found to be expressed in epithelial cells of acini and/or ducts as well as the stromal cells. Moreover, 17beta-HSD type 2 and EST1E1, two enzymes which inactivate E2, have been also localized in the same cell types. The present results indicate the enzymes which play a role in the synthesis and metabolism of E2 are expressed in both epithelial and stromal cells in human breast.
Li
Zhuo
Z
Oncology and Molecular Endocrinology Research Center, Laval University Hospital Research Centre (CRCHUL) and Laval University, Quebec City, Quebec, Canada.
Luu-The
Van
V
Poisson-Paré
David
D
Ouellet
Johanne
J
Li
Songyun
S
Labrie
Fernand
F
Pelletier
Georges
G
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001141:Aromatase / Q000378:metabolism*; D001940:Breast / Q000201:enzymology* / Q000378:metabolism; D004958:Estradiol / Q000138:chemical synthesis / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D017697:Premenopause; D043266:Steryl-Sulfatase / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D055815:Young Adult
D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human; D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D043266:Steryl-Sulfatase