Fatty acids derived from royal jelly are modulators of estrogen receptor functions.

ABSTRACT: 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? but not ER?, while in presence of E(2) FAs modulated both ER? and ER?. Moreover, in presence of FAs, the E(2)-induced recruitment of the EAB1 co-activator peptide to ER? 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? but not ER?, while in presence of E(2), FAs inhibited ERE-activity by both ER? and ER?. Molecular modeling revealed favorable binding of FAs to ER? at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ER? or ER?. 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?, ER? and co-activators to target genes.

SUBMITTER: Moutsatsou P 

PROVIDER: S-EPMC3008742 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature