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Characterization of a novel endogenous steroid, estradienolone (ED), in human pregnancy

Estradienolone (ED, 17beta-hydroxy-[1,5]-estradien-3-one) is a novel steroid hormone identified in pregnant women. It is an isomer of estradiol which binds the progesterone receptor and sex hormone binding globulin with high affinity. Since levels of ED remain high throughout pregnancy and decrease in association with term or preterm labour, ED may be involved in the maintenance of pregnancy. The objectives of the present study were to, (i) purify ED from pregnancy samples in quantities sufficient for chemical analysis to confirm its structural features, and (ii) identify its binding proteins and receptors. Our results show that ED binds the novel methyltrienolone (R1881) binding protein of JEG-3 cells with higher affinity than any other natural steroids tested. Furthermore, ED is able to inhibit transcriptional activity of the estrogen-receptor-related receptors alpha and gamma, suggesting that ED may be the natural ligand of these orphan receptors. ED is also able to activate the xenobiotic receptor SXR. Chemical analysis of the fine structural features of purified ED is in progress.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82297
Date January 2003
CreatorsNegi, Ranuka
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Division of Surgical Research.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 002499635, proquestno: AAIMR12508, Theses scanned by UMI/ProQuest.

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