Responsiveness to estradiol-17β and to phytoestrogens in primary human osteoblasts is modulated differentially by high glucose concentration

Dalia Somjen, Sara Katzburg, Fortune Kohen, Batya Gayer, Orly Sharon, David Hendel, Alvin M. Kaye

Research output: Contribution to journalArticlepeer-review

Abstract

We have reported previously, that female-derived bone cells responded to 17β-estradiol (E2) and to raloxifene (Ral), whereas male-derived cells responded only to dihydrotestosterone (DHT) when the stimulation of creatine kinase specific activity (CK), which is a marker for hormone responsiveness, was measured. In cells derived from pre-menopausal women, E2, G, D and Ral stimulated CK to higher extent compared to post-menopausal bone cells, whereas quecertin (Qu), carboxy-biochainin A (cBA) and carboxy-genistein (cG) stimulated CK in both age groups similarly, and biochainin A (BA) stimulated post-menopausal cells to a bit higher extent than pre-menopausal cells. Since the skeletal protective effects of estrogens are not discernable in diabetic women, we tested in this study, the effects of high glucose concentration in the growth medium, on the effects of estrogenic compounds on CK in human-derived bone cells (hObs). Female-derived hObs were grown either in normal (4.5 g/l; 22 mM, NG) or high glucose (9.0 g/l; 44 mM, HG) for 7 days. HG increased constitutive CK, but attenuated E2- and DHT-induced CK in female or male hObs, respectively. HG also inhibited genistein (G) and daidzein (D) stimulated CK in female hObs, but not the effects of biochainin A (BA), quecertin (Qu) or Ral. Intracellular, mainly nuclear binding of 3[H]E2 was characteristic of the different phytoestrogens in female hObs, was abolished by HG. Membranal binding of Eu-Ov-E2, was displaced only by E2-Ov, ICI, cG-Ov or cD-Ov but decreased total binding of Eu-Ov-E2 in both age groups and completely abolished the competition with E2-Ov or ICI in both age groups, but the competition with cD-Ov and cG-Ov was decreased only slightly but not statistically significant. HG also abolished Eu-BSA-T, which bound similarly male-derived hObs. All hObs expressed mRNA for ERα and ERβ with higher abundance of ERα. HG increased mRNA for both ERs in female-derived hObs, but decreased mRNA for both ERs in male-derived hObs. Hence, human bone cells, which express specific nuclear and membranal binding sites for estrogenic compounds, are modulated by HG, leading to altered hormonal responsiveness, which might block important effects of estrogenic compounds, contributing probably to their decreased skeletal preserving properties under hyperglycemia.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume99
Issue number2-3
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • Creatine kinase
  • Estrogen receptors α and β
  • Human primary osteoblasts
  • Hyperglycemia
  • Phytoestrogens
  • Sex and age specificity

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