SEX-HORMONES MEDIATE INTERLEUKIN-1-BETA PRODUCTION BY HUMAN OSTEOBLASTIC HOBIT CELLS

The mechanisms by which the sex hormones achieve their bone-sparing ef fects remains unresolved. Interleukin-1 beta (IL-1 beta) is an autocri ne/paracrine regulator of bone that may be produced in an estrogen-sen sitive manner. The regulation of IL-1 beta production by the gonadal s teroids was tested in the human osteoblastic HOBIT cell model. Dose-de pendent 4-8-fold increases (P < 0.05) in IL-1 beta mRNA levels followe d a 6-48 h treatment with 17 beta-estradiol or testosterone. Receptor mediation of these responses was indicated by experiments using 17 alp ha-estradiol or flutamide. Tumor necrosis factor-alpha (TNF) dependent increases in IL-1 beta mRNA levels were additive to the effects of th e steroids. Testosterone and TNF increased IL-1 beta protein release ( P < 0.05) while 17 beta-estradiol had little effect on release. The bo ne-sparing effects of the gonadal steroids may be accomplished, in par t, through their mediation of local IL-1 beta production.