Regulation of insulin-like growth factor-I and binding protein-3 expression in oMtla-oGH transgenic mice.
Growth hormone (GH)-transgenic mice provide a model for studying hormonal regulation of gene products responsible for efficient lean growth. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (BP-3) are two products involved in mediating the growth promoting actions of GH. Mice carrying the ovine metallothionein la-ovine growth hormone (oMtla-oGH) transgene were used to study GH regulation of IGF-I and BP-3 expression because these mice do not exhibit elevated basal oGH levels without transgene stimulation by exogenous zinc. C57B1/6XCBA mice with (transgenic = TG) and without control = C) the oMtla-oGH transgene were activated (+ Zn) or inactivated (-Zn) by the addition or removal of 25 mM zinc sulfate in the drinking water. Plasma IGF-I and BP-3 levels were determined by radioimmunoassay and western ligand blotting, respectively. Hepatic IGF-I and BP-3 mRNA levels were determined by slot-blot analysis. TG+Zn mice had higher plasma IGF-I (p < 0.05) and hepatic IGF-I mRNA (p < 0.05) levels as compared to TG-Zn, C+Zn and C-Zn mice. Plasma IGF-I and hepatic IGF-I mRNA levels in TG-Zn mice were not different from C+Zn and C-Zn mice. Removal of Zn decreased hepatic IGF-I mRNA levels to C levels in TG mice. Plasma BP-3 and hepatic BP-3 mRNA levels in TG+Zn mice were increased (p < 0.05) as compared to TG-Zn, C-Zn and C+Zn. Plasma BP-3 and hepatic BP-3 mRNA levels did not differ between TG-Zn, C-Zn and C+Zn mice. Expression of the transgene also increased the level of plasma BP-3 during pregnancy as compared to that observed for pregnant C mice. We conclude that oGH regulates IGF-I and BP-3 expression in the oMtla-oGH transgenic mouse model system.
Chow
J C
JC
Department of Animal Science, School of Veterinary Medicine, University of California-Davis 95616.
Murray
J D
JD
Pomp
D
D
Baldwin
R L
RL
Calvert
C C
CC
Oberbauer
A M
AM
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D013006:Growth Hormone / Q000235:genetics; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000737:chemistry; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep; D015032:Zinc / Q000378:metabolism
D002352:Carrier Proteins; D006131:Growth Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008668:Metallothionein; D015032:Zinc