Decreased acid-labile subunit (ALS) levels by endotoxin in vivo and by interleukin-1beta in vitro.
(1998) Growth Hormone & I G F Research — Vol. 8, n° 3, p. 217-223 (1998)
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- Authors
Thissen, Jean-Paul 
- Abstract
- The production by the liver of the three subunits of the growth hormone (GH)-dependent 150 kDa complex (IGF-I, IGF-binding protein-3 and acid-labile subunit or ALS) is primarily under the control of GH. Recent data have shown that, besides GH, endotoxin (LPS) and cytokines may regulate the liver IGF-I gene. To investigate the potential regulation of ALS by LPS, we measured serum ALS by immunoblot, 5 and 10 h after IP injection of LPS (250 or 750 microg/100 g BW vs saline), in 4-week-old female Wistar rats (four per group). Ten hours after injection, serum ALS levels were reduced by 57% (delta%) with the lower dose (P<0.05) and by 81% with the higher dose (P<0.01) by comparison with saline-treated rats. The decrease in ALS levels in response to LPS was not prevented by exogenous GH. To investigate the role of interleukin (IL)-1beta in the regulation of ALS, primary cultured rat hepatocytes were exposed to increasing concentrations of IL-1beta. Cell exposure to IL-1beta markedly decreased both basal and GH-stimulated ALS levels (-70%; P<0.01) in a dose-dependent fashion, with the half-maximal inhibitory effect at concentrations of 0.1 ng/ml. Our results show that endotoxin induces a rapid decline in circulating ALS that is potentially mediated through IL-1beta. By limiting the formation of the 150 kDa complex, this reduction in circulating ALS might contribute to the rapid decline in serum IGF-I observed in sepsis.
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Citations
Barreca, A., Ketelslegers, J.-M., Arvigo, M., Minuto, F., & Thissen, J.-P. (1998). Decreased acid-labile subunit (ALS) levels by endotoxin in vivo and by interleukin-1beta in vitro. Growth Hormone & I G F Research, 8(3), 217-223. https://doi.org/10.1016/S1096-6374(98)80114-7 (Original work published 1998)