title: IL-6-overexpression brings about growth impairment potentially through a GH receptor defect.
abstract: This paper is concerned with growth retardation associated with overproduction of interleukin-6 (IL-6). As a model, we used MUP/hIL-6 transgenic mice in which human IL-6 cDNA is overexpressed under the control of a MUP gene enhancer/promoter. The growth-retardation of MUP/hIL-6 transgenic mice was paralleled by reduced serum levels of IGF-I. As shown, hepatic IGF-I mRNA levels were reduced in the transgenic mice. MUP/hIL-6 transgenic mice are in a state of growth hormone (GH)-resistance, since their serum GH levels are either normal or elevated. To identify possible steps in GH signaling which might be perturbed in the transgenic mice, we examined the synthesis of GH receptor (GHR) mRNA. We noted a twofold reduction of hepatic GHR mRNA in the transgenic mice. We therefore conclude that overexpression of IL-6 brings about growth impairment in part through a GH receptor defect.
authors.affiliation: Department of Developmental and Structural Biology, Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Lieskovska
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.forename: Eva
authors.initials: E
authors.lastname: Derman
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D013006:Growth Hormone / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000254:growth & development; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein