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Studies on the effect of neonatal hypermetabolism on hypothalamo-pituitary-thyroid axis in adult rats
Insights
Neonatal exposure to 2,4-dinitrophenol (DNP) or L-thyroxine (T4) impairs the hypothalamo-pituitary-thyroid axis into adulthood. This hypermetabolism leads to growth retardation and reduced thyroid function.
Area of Science:
- Endocrinology
- Developmental Biology
- Toxicology
Background:
- Neonatal exposure to metabolic disruptors can have long-term effects on endocrine function.
- The hypothalamo-pituitary-thyroid (HPT) axis is crucial for growth and metabolism and is sensitive to early-life insults.
Purpose of the Study:
- To investigate the long-term effects of neonatal exposure to 2,4-dinitrophenol (DNP) and L-thyroxine (T4) on the HPT axis in adult rats.
- To compare the impact of hypermetabolism induced by DNP versus direct thyroid hormone administration.
Main Methods:
- Neonatal rats were injected daily with DNP or T4 from birth for 7 days.
- Saline-injected rats served as controls.
- Adult rats were assessed for growth, and plasma levels of thyroid-stimulating hormone (TSH) were measured after thyrotropin-releasing hormone (TRH) and propylthiouracil (PTU) challenges.
Main Results:
- Both DNP and T4 treated rats exhibited growth retardation compared to controls.
- TSH response to TRH and PTU challenges was blunted in both DNP and T4 groups.
- Pituitary TSH content decreased in T4-treated rats but not in DNP-treated rats.
- Hypothalamic alterations appeared more pronounced in T4-treated rats.
Conclusions:
- Neonatal hypermetabolism, induced by DNP or T4, results in long-term hypofunction of the pituitary-thyroid axis.
- The observed effects suggest that early-life metabolic disturbances can lead to persistent endocrine dysfunction.
- Hypothalamic involvement may differ depending on the nature of the neonatal insult.
Abstract:
Neonatal rats which had received a daily injection of 50 microgram of 2,4-dinitrophenol (DNP) or 30 microgram of L-thyroxine (T 4) for 7 days beginning on the day of birth were compared as to the late effect of the hypothalamo-pituitary-thyroid axis with the neo saline control. Neo DNP rats and neo T 4 rats revealed the retardation of growth compared with neo saline rats. The plasma level of TSH in both groups presented its low response following TRH administration. Furthermore, plasma TSH levels following the challenge of PTU were depressed in both neo DNP and neo T 4 rats compared with neo saline control rats. A small dose of T 4 injection, however, did not bring any difference on plasma TSH levels between neo T 4 and neo saline control rats while neo DNP rats showed a little blunted response of pituitary compared with neo T 4 and neo saline rats. Pituitary contents of TSH in neo T 4 rats decreased, but not in neo DNP rats. These results suggest that neonatal hypermetabolism causes the hypofunction of pituitary-thyroid axis through adult life and that the alteration of hypothalamus may be more obvious in neo T 4 rats than in neo DNP rats.