Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice

Wen Y. Chen, Michael E. White, Thomas E. Wagner, John J. Kopchick

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

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 litter-mates. 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.

Original languageEnglish (US)
Pages (from-to)1402-1408
Number of pages7
JournalEndocrinology
Volume129
Issue number3
DOIs
StatePublished - Sep 1991

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