Monday, January 03, 2011
PLoS ONE, 5(12), December 22, 2010
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 (E2), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ERβ but not ERα, while in presence of E2 FAs modulated both ERβ and ERα. Moreover, in presence of FAs, the E2-induced recruitment of the EAB1 co-activator peptide to ERα is masked and the E2-induced estrogen response element (ERE)-mediated transactivation is inhibited.
In HeLa cells, in absence of E2, FAs inhibited the ERE-mediated transactivation by ERβ but not ERα, while in presence of E2, FAs inhibited ERE-activity by both ERβ and ERα. Molecular modeling revealed favorable binding of FAs to ERα at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ERα or ERβ.
In KS483 osteoblasts, FAs, like E2, 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 E2, mediate estrogen signaling, at least in part, by modulating the recruitment of ERα, ERβ and co-activators to target genes…
In this study, we determined the possible estrogenic/antiestrogenic properties of 10H2DA, 3,10DDA and SA, isolated from RJ and identified by spectroscopic methods . In choosing the concentrations we considered 1) the commonly used RJ dietary supplementation (1–3 g daily), 2) the concentration of 10H2DA and the concentration of sebacic acid in RJ (3–6% and 0.5% respectively) , , 3) the concentration of 10H2DA, sebacic acid and 3,10 DDA as well as 10HDA acid in marketed RJ samples in Greece (40–50%, 5%, 4% and 20% respectively), 4) the human blood volume and bioavailability. Based on the above information, we decided to examine the biological effects of FAs in a concentration range of 10−10 M–10−5 M, which are physiologically achievable concentrations.