Growth hormone action in hypothyroid infant rats.
In neonatal rats, expression of serine protease inhibitors 2.1 and 2.3 mRNA peaks on d 2 of life and declines shortly thereafter, coinciding with levels of circulating GH. To evaluate the role of GH in this increase and to test the hypothesis that GH is active in perinatal life, we studied GH action in a model of GH deficiency. Maternal/neonatal hypothyroidism with consequent GH deficiency was induced by methimazole administration to pregnant dams. The resultant hypothyroid neonates were treated at d 2 or 7 of age with GH or saline for 1 h before exsanguination. In d-7 neonates, but not at d 2, GH administration resulted in significant serine protease inhibitors 2.1 and 2.3 mRNA induction. This treatment did not result in increased production of either GH receptor or IGF-I mRNA at either age. There was a slight GH-independent increase in GH receptor and IGF-I mRNA expression by d 7. Electromobility shift assays using hepatic nuclear extracts from these neonates and the GH response element from the serine protease inhibitor 2.1 promoter showed signal transducer and activator of transcription 5 (Stat5) binding in response to GH in extracts from d-7 rats only. Immunoblots of these extracts showed twice as much Stat5 in the nuclei of d-7 treated neonates compared with d-2 treated neonates. We conclude that there is apparent insensitivity to GH treatment in d-2 neonates that remits by d 7 and that this remission correlates with increased abundance of GH receptor and Stat5.
Humbert
J T
JT
Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
Bergad
P L
PL
Masha
O
O
Stolz
A M
AM
Kaul
S
S
Berry
S A
SA
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007037:Hypothyroidism / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D015843:Serpins; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C091103:LOC299282 protein, rat; D008894:Milk Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors; C050936:Serpina3c protein, rat; D015843:Serpins; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone