Linked Life Data

7618191

Source:http://linkedlifedata.com/resource/pubmed/id/7618191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-8-24
pubmed:abstractText
Mifepristone (RU 486), used clinically for the termination of early pregnancy, and its acetyl and 13-retro (13 alpha) analogs show potent antiproliferative effects against estrogen-dependent human breast tumors and endometriosis. However, there has been no report on direct inhibition of aromatase by antiprogesterones. Aromatase inhibitors have been shown to be effective against estrogen-dependent breast cancer. We evaluated the inhibition of aromatase by various antiprogestins (ZK 112.993, ZK 98.734, ZK 114.043, ZK 98.299, and ZK 114.863). Human placental microsomes were incubated with [1 beta-3H,4-14C] androstenedione (3-114 nM) in the presence of NADPH, with or without putative inhibitors (10-200 microM). Aromatase activity was assessed by tritium release to water from the 1 beta-position of the substrate. ZK 112.993 and ZK 98.734 did not show any inhibitory effect. The statistical analysis of the data using standard errors was obtained from replicate experiments. ZK 114.043 showed slight inhibition with a Ki of 54.8 +/- 6.4 microM (m +/- SE, n = 6) against androstenedione aromatization. The two 13-retro-steroids, ZK 98.299 and ZK 114.863, showed aromatase inhibition with Ki values of 19.0 +/- 1.5 microM (n = 7) and 12.7 +/- 0.94 microM (n = 7), respectively, which is weak with respect to some known potent inhibitors, but significant when compared with the other antiprogestins which were tested. The results suggest that the unnatural 13-retro-antiprogestin conformation may have a better fit to the aromatase active site than the natural 13 beta-antiprogestin conformation. (Steroids 60:234-238, 1995).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
234-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inhibition of aromatase activity in human placental microsomes by 13-retro-antiprogestins.
pubmed:affiliation
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, New York, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't