Human cultured female osteoblasts (Obs) respond age-dependently to estradiol-17Î² (E2) and to phytoestrogens by increased DNA synthesis (DNA) and creatine kinase specific activity (CK). ERÎ± mRNA expression is higher than ERÎ² mRNA in Obs. Pre-menopausal Ob (prOb) reveals higher expression of ERÎ± than post-menopausal Ob (poOb), but similar intracellular and membranal E2 bindings. ERÎ± mRNA is stimulated in prOb and inhibited in poOb by different estrogens. ERÎ² mRNA in prOb is stimulated by 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERÎ² specific agonist) and 4,4',4"-[4-Propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERÎ± specific agonist) and raloxifene (Ral) and inhibited by genistein (G) and daidzein (D) while in poOb only E2 and DPN inhibited it. All phytoestrogenic carboxy- derivatives stimulated ERÎ± mRNA in both Ob, while the protein bound- carboxy were ineffective. All compounds except carboxybiochainin A (cBA) had no effect on ERÎ². There is higher expression of 1Î± 25 hydroxy- vitamin D (1OHase) mRNA in poOb, whereas 1,25(OH)2D3 (1,25) production is similar, but all compounds increased 1OHase mRNA and 1,25 to higher extent in prOb. Obs express 15 and 12 lipoxygenase (12LO and 15LO) mRNA and produce 12 and 15 HETE (12H and 15H). 12LO expression is higher and 15LO is lower in prOb, while 12H is higher in prOb and 15H is similar in both. Both LOs are increased to higher extent in poOb by all estrogens except Ral and PPT. 12H is increased by DPN, PPT and carboxy- derivatives similarly in both Obs, while 15H is increased by biochainin A (BA), Ral and carboxyderivatives. DNA synthesis and CK are stimulated by all compounds in both Obs, but to higher extent in prOb.
Age-Dependent Responsiveness of Human Female Cultured Bone Cells to Estrogenic Compounds: Dalia Somjen, Sara Katzburg, Alvin M. Kaye, Fortune Kohen and Gary H. Posner
Last date updated on July, 2014