Endocrinologia e Síndrome Metabólica
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Abstrato

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

Human cultured female osteoblasts (Obs) respond age-dependently to estradiol-17β (E2) and to phytoestrogens by increased DNA synthesis (DNA) and creatine kinase specific activity (CK). ERα mRNA expression is higher than ERβ mRNA in Obs. Pre-menopausal Ob (prOb) reveals higher expression of ERα than post-menopausal Ob (poOb), but similar intracellular and membranal E2 bindings. ERα mRNA is stimulated in prOb and inhibited in poOb by different estrogens. ERβ mRNA in prOb is stimulated by 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ specific agonist) and 4,4ʹ,4ʺ-[4-Propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα 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 ERα mRNA in both Ob, while the protein bound- carboxy were ineffective. All compounds except carboxybiochainin A (cBA) had no effect on ERβ. There is higher expression of 1α 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. The 1,25 less-calcemic analog JK 1624F2-2 (JKF) up-regulated DNA and CK response to all estrogens except BA and the carboxy- derivatives in both Obs. JKF stimulated intracellular binding of E2 similarly by all compounds except BA, but inhibited its membranal binding in both Obs. In conclusion Obs respond age-dependently to estrogens in a yet unknown mechanism and the beneficial outcome for human female bones is not yet clear.