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Effects of 17β-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-β1 and insulin-like growth factor-1 in primary human osteoblast cultures

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Abstract

We investigated the effects of 17β- estradiol and two selective estrogen receptor modulators, tamoxifen and raloxifene, on the expression and release of constitutive and interleukin- 1-stimulated interleukin (IL)-6, transforming growth factor-β1 (TGF-β1) and insulin-like growth factor-1 by osteoblasts in primary culture from trabecular bone of healthy post-menopausal women. After 24 h incubation with 10-8 M concentration of these compounds, there was no decrease in: a) the constitutive or IL-1β-induced levels of IL-6 protein released to culture medium; b) the constitutive IL-6 mRNA expression after incubation of osteoblasts with 10−8 M 17β- estradiol or 10−8 M tamoxifen for 1, 3, 6, 24 or 30 h. Although a decrease after 30 h of treatment with 10−8 M, raloxifene was found in mRNA IL-6 expression, and this fact was not reflected by a decrease in the release of IL-6 protein to the culture medium after 48 h of incubation with 10−8 M or 10−8 M raloxifene. Tumoral growth factorTGF-β1 expression was not influenced by incubation with these compounds. Gene expression of IGF-I increased following 24 or 30 h incubation with 10−8 M 17β-estradiol and 30 h incubation with raloxifene. Tamoxifen did not affect IGF-I expression. In conclusion, the effects of estradiol or tamoxifen on bone metabolism do not appear to be mediated through the regulation of osteoblast IL-6 release or synthesis, but raloxifene produces a decrease in mRNA IL-6 expression. The actions of estradiol, tamoxifen and raloxifene do not appear to be mediated by tumoral growth factor TGF-β1. On the other hand, an increase in IGF-I synthesis induced by raloxifene and estradiol could mediate, in part, the effects of these compounds on bone.

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Authors and Affiliations

  1. Fundación Jiménez Díaz, Laboratorio de Fisiopatología ósea, Avenida Reyes Católicos 2, 28040, Madrid, Spain

    C. Méndez-Dávila, C. García-Moreno & C. de la Piedra PhD

  2. Lilly Laboratories, Medical Department, San Sebastian de Los Reyes, Madrid, Spain

    C. Turbì

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  1. C. Méndez-Dávila
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Méndez-Dávila, C., García-Moreno, C., Turbì, C. et al. Effects of 17β-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-β1 and insulin-like growth factor-1 in primary human osteoblast cultures. J Endocrinol Invest 27, 904–912 (2004). https://doi.org/10.1007/BF03347531

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