Sex specific response of cultured human bone cells to ERα and ERβ specific agonists by modulation of cell proliferation and creatine kinase specific activity.

J Steroid Biochem Mol Biol

Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel.

Published: July 2011

AI Article Synopsis

  • The study investigates how human cultured bone cells (hObs) respond to estrogen, focusing on the sex-specific reactions to estrogen receptor (ER) α and ERβ agonists.
  • All cultured cells express mRNA for both ERs, with ERα being more responsive to estrogenic compounds in female hObs, while male hObs show no such response.
  • Treatments with various estrogenic compounds enhance DNA synthesis and creatine kinase activity in female hObs but not in males, highlighting different regulatory mechanisms at play driven by age and sex.

Article Abstract

We have previously reported that human cultured bone cells (hObs) respond to estradiol-17β (E2) by stimulating DNA synthesis, creatine kinase BB specific activity (CK) and other parameters sex-specifically. We now investigate the sex specificity of the response of these hObs to estrogen receptor (ER) α and ERβ specific agonists. Real time PCR revealed that all cells express mRNA for both ERs. ERα mRNA but not ERβ mRNA was stimulated by all estrogenic compounds in both pre- and post-menopausal hObs with no effect in male hObs. Cells treated with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ specific agonist) and 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα specific agonist) showed increased DNA synthesis and CK in all female but not male hObs. Raloxifene (Ral), a specific ERα antagonist, inhibited the stimulation of DNA synthesis and CK by E2 or PPT, but not by DPN. DPN and PPT like E2 modulated the expression of both 12 and 15 lipooxygenase (LO) mRNA in both female but not male hObs. 12 and 15 HETE production was modulated only by DPN and PPT in these cells. The LO inhibitor baicaleine inhibited only E2 and PPT but not DPN effects in both female hObs. In conclusion, we provide herein evidence for the separation of age- and sex-dependent mediation via both ERα and ERβ pathways in the effects of estrogens on hObs, with a yet unknown mechanism.

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http://dx.doi.org/10.1016/j.jsbmb.2011.03.006DOI Listing

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