Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice.
A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.
Chen
W Y
WY
Department of Zoology, Ohio University, Athens.
White
M E
ME
Wagner
T E
TE
Kopchick
J J
JJ
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004392:Dwarfism / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006128:Growth / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D011869:Radioligand Assay; D011986:Receptors, Somatotropin / Q000378:metabolism*
D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone