Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow.
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.
Lin
S C
SC
Division of Endocrinology, University of Arkansas for Medical Sciences Center for Osteoporosis and Metabolic Bone Diseases, Little Rock, AR 77205, USA.
Yamate
T
T
Taguchi
Y
Y
Borba
V Z
VZ
Girasole
G
G
O'Brien
C A
CA
Bellido
T
T
Abe
E
E
Manolagas
S C
SC
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010052:Ovariectomy; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000187:drug effects
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D013196:Dihydrotestosterone; D004958:Estradiol