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

J Clin Invest. 1997 Oct 15;100(8):1980-90. doi: 10.1172/JCI119729.


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 17beta-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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / drug effects*
  • Bone Marrow Cells / drug effects
  • Cells, Cultured
  • Connective Tissue Cells / drug effects*
  • Dihydrotestosterone / pharmacology*
  • Estradiol / pharmacology*
  • Female
  • Gene Expression Regulation
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Mice
  • Osteoblasts / drug effects
  • Ovariectomy
  • Receptors, Interleukin-6 / biosynthesis*
  • Receptors, Interleukin-6 / genetics
  • Stromal Cells / drug effects


  • Interleukin-6
  • Receptors, Interleukin-6
  • Dihydrotestosterone
  • Estradiol