Phytoestrogenic Compounds and Their Synthetic Analogs, Contrary to Estradiol- 17b Stimulates Human Derived Female Cultured Bone Cells in Hyperglycemic Conditions

D Somjen,S Katzburg,D Hendel,S Tamir,O Sharon

doi:10.4172/2157-7536.1000105

Abstract

Cultured female- derived human osteoblasts (hObs) responded by different parameters to the phytoestrogens: daidzein (D), glabrene (Gla) and glabridin (Glb), to their synthetic derivatives; carboxy-daidzein (cD) and to estradiol- 17? (E2). Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested the effects of these compounds on hObs grown in growth medium with high glucose (HG; 9.0g/L; 44 mM) compared to normal glucose (NG; 4.5g/L; 22 mM) using the stimulation of creatine kinase specific activity (CK) and 3[H] thymidine incorporation in to DNA (DNA) as hormonal responsiveness markers. HG slightly increased DNA and CK in hObs. Stimulations by E2 was abolished and by cD and D was slightly decreased in HG, but not by Gla and Glb in both age groups. Growing hObs in HG upregulated the expression of mRNA of both ER? and ER? in cells from pre- but not from post-menopausal women. Cells from both age groups express also mRNA for 25 hydroxy vitamin D3 1-? hydroxylase and showed enzymic activity which were down-regulated by HG in both age groups. Whether Gla and Glb act differentially via ERs and/or 1-? hydroxylase is not yet established.Since these compounds are active even in HG, they might be used for treating hyperglycemic/diabetic women.

Highlights

We have previously studied the effects of estrogens on bone in a rat model [1,2,3] using the increase in the specific activity of creatine kinase as a response marker
Female derived human osteoblasts (hObs) treated with E2, Gla, Glb, cD or D for 24 h, showed a significant increase in creatine kinase (CK) specific activity in both age groups (Figure 2)
Growth of the cells in high glucose led to abolishment of the response of DNA synthesis to treatment with E2, slightly reduction in the response to cD or D but did not change the response to Gla or Glb cells from both age groups (Figure 3)

Summary

Introduction

We have previously studied the effects of estrogens on bone in a rat model [1,2,3] using the increase in the specific activity of creatine kinase as a response marker. The brain type (BB) isoenzyme of creatine kinase (CK) which is part of the “energy buffer” system, regulates the cellular concentration of ATP and ADP, is the major component of the “E2induced protein” of rat uterus [4] and is an efficient response marker to detect activity of E2 as well as other estrogenic compounds, in bone cells in vivo and in vitro [1,5] which contain low concentrations of E2 receptors [6,7]. The effect of estrogen in the different tissues is initiated by its binding to estrogen receptors (ERs). New compounds, which can replace current hormone replacement therapy treatments with no such deleterious effects, are highly desirable [11]

Methods

Results

Conclusion