STUDIES ON THE EFFECT OF NEONATAL HYPERMETABOLISM ON HYPOTHALAMO-PITUITARY-THYROID AXIS IN ADULT RATS
1978 Volume 28 Issue 2 Pages 105-122
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1978 Volume 28 Issue 2 Pages 105-122
It has been reported that large dose of sodium L-thyroxine (T4) administration to the neonatal rats produces persistent alterations in hypothalamo-pituitary-thyroid axis on adult rats. The neonatal animals treated with T4 exhibited retarded growth and produced a variety of endocrine abnormalities through the course of adult life. Thus this group of abnormalities has been called as neo T4 syndrom. These neo T4 rats, however, were injected with 15-30μ g of T4 daily during the first 7days of life. It is clear that such large dose of T4 administration produces severe hypermetabolic situations on neonatal animals as indicated by the increase of oxgen consumption, elevation of body temperature, increased basal metabolic rate and so much caloric consumption. Although it is generally accepted that metabolic disorders in neonatal period modify various endocrine and central nervous system, disagree exsists whether these kinds of abnormalities are specific for neo T4 syndrome or not. 2, 4-Dinitrophenol (DNP) has been recognized as an agent of inducing hypermetabolism in various animals by virture of its uncoupling effect on oxidative phospholyration with the Krebs tricarboxylic acid cycle.
It is also well known that administration of DNP decreases plasma PBI levels and produces T4 displacement from serum protein. We employed DNP in our study to produce hypermetabolism on neonatal rats. Our present study was undertaken to compare DNP treated neonatal rats (neo DNP) with neo T4 rats and to compare both of groups to neo saline rats as control to see the effect of neonatal hypermetabolism on the hypothalamo-pituitary-thyroid axis in adult stage. Neonatal rats which had received 7daily injection of 50μ g of DNP or 30μ g of L-T4beginning with the day of birth were used in the present study.
The following results were obtained ;
1) Neo DNP and neo T4 rats revealed persistent retardation of growth compared with neo saline rats.
2) Neo T4 rats at 22days of age showed low plasma T4 and T3 levels compared with neo saline control rats but neo DNP rats did not show it.
3) Neo DNP and neo T4 rats at 22days of age showed lower response to synthetic TRH administration (I.P) than that of neo saline rats. Moreover neo T4 rats showed almost no response to TRH.
4) Neo DNP and neo T4 rats at 22days of age showed low pituitary TSH contents compared to neo saline rats and also neo T4 rats showed apparently high pituitary prolactin contents compared with neo saline rats but neo DNP rats did not show it.
5) Neo DNP and neo T4rats in adult stage showed also blunted response to TRH administration (I, V) compared with neo saline rats.
6) Neo DNP and neo T4rats in adult stage showed abnormal response to PTU or T4 administration.
7) Neo T4 rats at 161days of age showed lower pituitary TSH contents and endocrine organ weights than neo saline and neo DNP rats.
Thus, the present study has shown that neonatal hypermetabolism causes hypofunction of pituitary-thyroid axis through adult life and that alternation of hypothalamus may be more prominent in neo T4 rats than neo DNP rats.
