Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth.
To study the role of insulin-like growth factor I (IGF-I) in mediating the growth-promoting function of GH, IGF-I expression was assayed in transgenic mice carrying either GH or GRF fusion genes. These mice exhibit enhanced growth as a result of high level ectopic expression of GH and have 2-fold elevation of both hepatic IGF-I mRNA levels and circulating IGF-I levels. Hepatic IGF-I mRNA levels are low at birth regardless of GH levels; they increase approximately 10-fold during postnatal development and become GH inducible 2 weeks after birth. The ontogeny of circulating IGF-I is similar. Accelerated growth in transgenic mice with GH fusion genes commences 3 weeks after birth despite high circulating GH levels at least as early as birth. In addition, endogenous mouse GH-secreting somatotroph cells in the pituitary are present in normal numbers at 3 weeks, but are undetectable 4 weeks after birth. Because the time at which IGF-I expression becomes GH responsive slightly precedes both the initiation of accelerated growth and the time when endogenous GH disappears, we conclude that IGF-I is directly involved in mediating the GH signal and that delayed induction of IGF-I gene expression is responsible, at least in part, for the delayed onset of other GH-responsive events.
Mathews
L S
LS
Department of Biochemistry, University of Washington, Seattle 98195.
Hammer
R E
RE
Brinster
R L
RL
Palmiter
R D
RD
D000375:Aging; D000818:Animals; D003001:Cloning, Molecular; D005796:Genes; D013006:Growth Hormone / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000254:growth & development*; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000254:growth & development*; D010902:Pituitary Gland / Q000254:growth & development*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008668:Metallothionein