Linked Life Data

15748827

Source:http://linkedlifedata.com/resource/pubmed/id/15748827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-3-7
pubmed:abstractText
Although ovaries serve as the primary source of estrogen for pre-menopausal women, after menopause estrogen biosynthesis from circulating precursors occurs in peripheral tissues by the action of several enzymes, 17beta-hydroxysteroid dehydrogenase 1 (17beta-HSD1), aromatase and estrogen sulfatase. In the breast, both normal and tumoral tissues have been shown to be capable of synthesizing estrogens, and this local estrogen production can be implicated in the development of breast tumors. In these tissues, estradiol (E(2)) can be synthesized by three pathways: (1) estrone sulfatase transforms estrogen sulfates into bioactive estrogens, (2) 17beta-HSD1 converts estrone (E(1)) into E(2), (3) aromatase which converts androgens into estrogens is also present and contributes to the in situ synthesis of active estrogens but to a far lesser extent than estrone sulfatase. Quantitative assessment of E(2) formation in human breast tumors indicates that metabolism of estrone sulfate (E(1)S) via the sulfatase pathway produces 100-500 times more E(2) than androgen aromatization. Breast tissue also possesses the estrogen sulfotransferase involved in the conversion of estrogens into their sulfates that are biologically inactive. In the present review, we summarized the action of the 19-nor-progestin nomegestrol acetate (NOMAC) on the sulfatase, 17beta-HSD1 and sulfotransferase activities in the hormone-dependent MCF-7 and T47-D human breast cancer cell lines. Using physiological doses of substrates NOMAC blocks very significantly the conversion of E(1)S to E(2). It inhibits the transformation of E(1) to E(2). NOMAC has a stimulatory effect on sulfotransferase activity in both cell lines, with a strong stimulating effect at low doses but only a weak effect at high concentrations. The effects on the three enzymes are always stronger in the progesterone-receptor rich T47-D cell line as compared with the MCF-7 cell line. Besides, no effect is found for NOMAC on the transformation of androstenedione to E(1) in the aromatase-rich choriocarcinoma cell line JEG-3. In conclusion, the inhibitory effect provoked by NOMAC on the enzymes involved in the biosynthesis of E(2) (sulfatase and 17HSD pathways) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive E(1)S, can open attractive perspectives for future clinical trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/17-Hydroxysteroid Dehydrogenases, http://linkedlifedata.com/resource/pubmed/chemical/3 (or 17)-beta-hydroxysteroid..., http://linkedlifedata.com/resource/pubmed/chemical/Aromatase, http://linkedlifedata.com/resource/pubmed/chemical/Estradiol, http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, http://linkedlifedata.com/resource/pubmed/chemical/Estrone, http://linkedlifedata.com/resource/pubmed/chemical/Megestrol, http://linkedlifedata.com/resource/pubmed/chemical/Norpregnadienes, http://linkedlifedata.com/resource/pubmed/chemical/Progesterone Congeners, http://linkedlifedata.com/resource/pubmed/chemical/Progestins, http://linkedlifedata.com/resource/pubmed/chemical/Sulfatases, http://linkedlifedata.com/resource/pubmed/chemical/Sulfotransferases, http://linkedlifedata.com/resource/pubmed/chemical/estrone sulfatase, http://linkedlifedata.com/resource/pubmed/chemical/estrone sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/nomegestrol acetate
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells.
pubmed:affiliation
Non-Clinical Research and Development Department, Théramex, 6 Avenue Prince Héréditaire Albert, 98000, Monaco. jshields@theramex.mc
pubmed:publicationType
Journal Article, Comparative Study, Review