Linked Life Data

11557270

Source:http://linkedlifedata.com/resource/pubmed/id/11557270

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-9-14
pubmed:abstractText
Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
427
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11557270-Animals, pubmed-meshheading:11557270-Binding, Competitive, pubmed-meshheading:11557270-Contraceptive Agents, Female, pubmed-meshheading:11557270-Dose-Response Relationship, Drug, pubmed-meshheading:11557270-Estradiol, pubmed-meshheading:11557270-Estrogen Antagonists, pubmed-meshheading:11557270-Estrogens, pubmed-meshheading:11557270-Female, pubmed-meshheading:11557270-Humans, pubmed-meshheading:11557270-Levonorgestrel, pubmed-meshheading:11557270-Pituitary Gland, Anterior, pubmed-meshheading:11557270-Rats, pubmed-meshheading:11557270-Rats, Wistar, pubmed-meshheading:11557270-Receptors, Estrogen, pubmed-meshheading:11557270-Receptors, Progesterone, pubmed-meshheading:11557270-Recombinant Fusion Proteins, pubmed-meshheading:11557270-Saccharomyces cerevisiae, pubmed-meshheading:11557270-beta-Galactosidase
pubmed:year
2001
pubmed:articleTitle
Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.
pubmed:affiliation
Department of Reproductive Biology, National Institute of Medical Sciences and Nutrition S. Zubirán, Vasco de Quiroga 15, Mexico City, C.P. 14000, Mexico.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't