Cultured female-derived human bone cells (hObs) responded by different parameters to different phytoestrogenic and vitamin D compounds. Pre- and post-menopausal hObs express ERα and ERβ mRNA with higher abundance of ERα. Pre-treatment with the less-calcemic vitamin D analog JKF 1624F 2-2 (JKF) upregulated responsiveness to estrogens via modulation of ERs expression. These estrogenic compounds induce the expression and activity of 25 hydroxy-vitamin D 3-1α hydroxylase (1OHase). We now analyzed the effects of carboxy-genistein (cG), carboxy-biocainin A (cBA) and carboxy-daidzein (cD), of BA, D or G and of licorice derived compounds glabridin (Glb) and glabrene (Gla) and estradiol-17β (E 2) on DNA synthesis, creatine kinase specific activity (CK), intracellular and membranal E 2 binding and their modulations by JKF in hObs. We also analyzed modulation by phytoestrogenic compounds of 1OHase mRNA expression and activity. We showed that: (1) all compounds stimulated DNA synthesis and CK. (2) JKF and all estrogenic compounds modulated ERα and ERβ mRNA expression. (3) Pre-treatment with JKF increased DNA synthesis and CK responses only to E 2, D, G and Gla. (4) JKF increased the intracellular competitive binding only of E 2, D and G. (5) JKF abolished the membranal binding of all protein-bound estrogens. (6) JKF and all estrogenic compounds except the protein-bound ones up-regulated 1OHase expression and activity. In conclusion phytoestrogens and their analogs increase DNA synthesis and CK, and lead to increased production of 1,25(OH) 2D 3 in hObs, while pre-treatment with JKF modulates the effect of estrogenic compounds via regulation of ERs mRNA expression in a yet unclear mechanism.
|Number of pages||7|
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|State||Published - Nov 2011|
- Creatine kinase
- DNA synthesis
- Human female bone cells
- Less-calcemic vitamin D analogs