期刊
PLOS ONE
卷 5, 期 12, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0015594
关键词
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资金
- Greek General Secretariat of Research and Technology
- Bodossaki Foundation
- Gaea Products SA
- Aktina SA
- Yiotis SA
- Pierre Fabre Hellas
- Bee Culturing Co Attiki Alex Pittas
- Korres SA [EPAN-TP27, PENED-70-3-6340, PAVE-70-3-8966]
- Swedish Research Council [08-0573, 621-2006-4470]
- Marie Curie Outgoing International Fellowships [MOIF-CT-2006-040428]
Royal jelly (RJ) excreted by honeybees and used as a nutritional and medicinal agent has estrogen-like effects, yet the compounds mediating these effects remain unidentified. The possible effects of three RJ fatty acids (FAs) (10-hydroxy-2-decenoic-10H2DA, 3,10-dihydroxydecanoic-3,10DDA, sebacic acid-SA) on estrogen signaling was investigated in various cellular systems. In MCF-7 cells, FAs, in absence of estradiol (E-2), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ER beta but not ER alpha, while in presence of E-2 FAs modulated both ER beta and ER alpha. Moreover, in presence of FAs, the E-2-induced recruitment of the EAB1 co-activator peptide to ER alpha is masked and the E-2-induced estrogen response element (ERE)-mediated transactivation is inhibited. In HeLa cells, in absence of E-2, FAs inhibited the ERE-mediated transactivation by ER beta but not ER alpha, while in presence of E-2, FAs inhibited ERE-activity by both ERb and ER alpha. Molecular modeling revealed favorable binding of FAs to ER alpha at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ER alpha or ER beta. In KS483 osteoblasts, FAs, like E-2, induced mineralization via an ER-dependent way. Our data propose a possible molecular mechanism for the estrogenic activities of RJ's components which, although structurally entirely different from E-2, mediate estrogen signaling, at least in part, by modulating the recruitment of ER alpha, ER beta and co-activators to target genes.
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