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 leve ls of circulating GH, To evaluate the role of GH in this increase and to te st the hypothesis that GH is active in perinatal life, we studied GH action in a model of GH deficiency. Maternal/neonatal hypothyroidism with consequ ent GH deficiency was induced by methimazole administration to pregnant dam s. 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 nor result in increased producti on, of either GH receptor or IGF-I mRNA at either age. There was a slight G H-independent increase in GH receptor and IGF-I mRNA expression by d 7. Ele ctromobility shift assays using hepatic nuclear extracts from these neonate s and the GH response element from the serine protease inhibitor 2.1 promot er showed signal transducer and activator of transcription 5 (Stat5) bindin g in response to GH in extracts from d-7 rats only. Immunoblots of these ex tracts showed twice as much Stat5 in the nuclei of d-7 heated neonates comp ared with d-2 treated neonates. We conclude that there is apparent insensit ivity to GH treatment in d-2 neonates that remits by d 7 and that this remi ssion correlates with increased abundance of GH receptor and Stat5.