Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow

Song Chang Lin, Tomoo Yamate, Yasuto Taguchi, Victoria Z.C. Borba, Giuseppe Girasole, Charles A. O'Brien, Teresita Bellido, Etsuko Abe, Stavros C. Manolagas

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105 Scopus citations

Abstract

Both estrogen and androgen exert their antiosteoporotic effects, at least in part, by inhibiting IL-6 production, thereby suppressing osteoclastogenesis. Several observations, however, suggest that besides increased IL-6 production, sensitivity of the osteoclastogenic process to this cytokine is altered after ovariectomy. Based on this and evidence that the ligand-binding subunit of the IL-6 receptor (gp80) is a limiting factor for the actions of IL-6 on bone, we hypothesized that sex steroids regulate expression of the IL-6 receptor as well. We report that 17β-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels. These effects did not require new protein synthesis. In contrast to sex steroids, parathyroid hormone stimulated gp130 expression; this effect was opposed by sex steroids. Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL- 6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR. The demonstration of increased expression of the IL-6 receptor after loss of sex steroids provides an explanation for why IL-6 is important for skeletal homeostasis in the sex steroid-deficient, but not replete, state.

Original languageEnglish (US)
Pages (from-to)1980-1990
Number of pages11
JournalJournal of Clinical Investigation
Volume100
Issue number8
DOIs
StatePublished - Oct 15 1997

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Keywords

  • Androgen
  • Cytokine receptors
  • Cytokines
  • Estrogen
  • Osteoporosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lin, S. C., Yamate, T., Taguchi, Y., Borba, V. Z. C., Girasole, G., O'Brien, C. A., Bellido, T., Abe, E., & Manolagas, S. C. (1997). Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow. Journal of Clinical Investigation, 100(8), 1980-1990. https://doi.org/10.1172/JCI119729