We have previously reported, that cultured female- derived human Osteoblats (hObs) responded to DT56a (Femarelle). Since the skeletal protective effects of estrogens are not discernible in diabetic women, we sought to test the effects of DT56a on hObs grown in high glucose concentration in the growth medium (HG) as compared to estradiol-17β (E2). We used the stimulation of creatine kinase specific activity (CK), and 3[H] thymidine incorporation into DNA (DNA synthesis), in response to E2 or DT56a as markers for treatment responsiveness. hObs were isolated from premenopausal and postmenopausal women. Cells were grown either in normal glucose (NG) (4.5 g/l; 22 mM) or HG (9.0 g/l; 44 mM) for 7 days. HG slightly increased DNA synthesis in hObs. In HG environment, the stimulation in response to E2 was decreased but not to DT56a in both age groups. Growing hObs in HG resulted in increased expression of both ERs (alpha and beta) mRNA in hObs from pre-menopausal but not in hObs from post-menopausal women. Pre-treatment of hObs with DT56a increased the expression of both ERs mRNA in hObs from both age groups. Pre-treatment of hObs with E2 increased expression of ERα mRNA in hObs from pre-menopausal women but inhibited it in hObs from post-menopausal women. Pre-treatment with E2 in hObs from both age groups inhibited ERβ mRNA expression.
Growing hObs in HG led to decrease of intracellular binding of 3[H] E2 in cells from both age groups when competed by E2 but not by DT56a.
This study shows that DT56a, contrary to E2, is active on hObs even in HG environment and, contrary to E2, activates ER even in HG environment, These findings suggest that Femarelle (DT56a) may be used as an effective treatment for the hyperglycemic/diabetic postmenopausal women.
30 Apr - 04 May 2011
European Society of Endocrinology