Abstract
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.
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Abbreviations
- Spi:
-
serine protease inhibitor
- GHR:
-
GH receptor
- GHBP:
-
GH-binding protein
- GHRE:
-
GH response element
- GHINF:
-
GH-inducible nuclear factor complex
- Stat:
-
signal transducer and activator of transcription
- EMSA:
-
electromobility shift assay
- PMSF:
-
phenylmethylsulfonyl fluoride
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Acknowledgements
The authors thank the Department of Pediatrics, University of Minnesota for support for J.T.H. to attend the National Medical Students Research Forum, where this work was presented in abstract form.
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Supported by National Institutes of Health grant DK32817 (S.A.B.) and student research fellowships (J.T.H.) from the Endocrine Society and the Minnesota Medical Foundation.
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Humbert, J., Bergad, P., Masha, O. et al. Growth Hormone Action in Hypothyroid Infant Rats. Pediatr Res 47, 250 (2000). https://doi.org/10.1203/00006450-200002000-00017
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DOI: https://doi.org/10.1203/00006450-200002000-00017
