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Growth hormone action in hypothyroid infant rats
J T Humbert1, P L Bergad, O Masha
1Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
Pediatric Research
|February 16, 2000
Summary
Growth hormone (GH) is inactive in 2-day-old rats but becomes active by day 7, coinciding with increased GH receptor and Stat5. This study reveals a critical developmental window for GH action in neonatal rats.
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Serine protease inhibitors (SPIs) 2.1 and 2.3 mRNA expression peaks early in neonatal rats, coinciding with circulating growth hormone (GH) levels.
- The role of GH in perinatal life and its developmental regulation remain incompletely understood.
Purpose of the Study:
- To investigate the role of GH in SPI mRNA induction during early neonatal development.
- To test the hypothesis that GH is active in perinatal life and to identify factors contributing to developmental changes in GH sensitivity.
Main Methods:
- A rat model of GH deficiency was induced via maternal/neonatal hypothyroidism using methimazole.
- Hypothyroid neonates were treated with GH or saline at postnatal days 2 or 7.
- SPI 2.1 and 2.3 mRNA levels, GH receptor, IGF-I mRNA, and signal transducer and activator of transcription 5 (Stat5) nuclear abundance were analyzed.
Main Results:
- GH administration induced SPI 2.1 and 2.3 mRNA in 7-day-old neonates but not in 2-day-old neonates.
- GH treatment did not increase GH receptor or IGF-I mRNA; however, a slight GH-independent increase in these was observed by day 7.
- Electromobility shift assays and immunoblotting demonstrated GH-dependent Stat5 binding and increased nuclear Stat5 abundance in 7-day-old neonates compared to 2-day-old neonates.
Conclusions:
- Neonatal rats exhibit apparent insensitivity to GH at day 2 of life, which resolves by day 7.
- This developmental remission of GH insensitivity correlates with increased GH receptor and nuclear Stat5 abundance, suggesting a critical window for GH action during early development.