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Effects of hypo- and hyperthyroidism on pancreatic TRH-degrading activity and TRH concentrations in developing rat
Insights
Thyroid hormone levels influence thyrotrophin-releasing hormone (TRH) and TRH-degrading activity (TRH-DA) in the developing rat pancreas. Thyroid status significantly alters pancreatic TRH concentrations and TRH-DA during the neonatal period.
Area of Science:
- Endocrinology
- Developmental Biology
- Pancreatic Physiology
Background:
- Neonatal rat pancreas exhibits high thyrotrophin-releasing hormone (TRH) concentrations that decrease postnatally.
- Pancreatic TRH-degrading activity (TRH-DA) emerges and matures during the early postnatal period.
- This developmental window is characterized by low circulating thyroid hormone levels.
Purpose of the Study:
- To investigate the impact of altered thyroid status on pancreatic TRH and TRH-DA during rat neonatal development.
- To elucidate the relationship between thyroid hormones and the regulation of pancreatic TRH and TRH-DA.
Main Methods:
- Induction of hypothyroidism using 6-n-propyl-2-thiouracil (PTU) and hyperthyroidism using triiodothyronine (T3) in neonatal rats.
- Measurement of pancreatic TRH concentrations and TRH-DA at various ages from birth to day 29.
- Comparison of treated animals with age-matched control rats.
Main Results:
- Hypothyroid rats showed persistently higher pancreatic TRH concentrations and lower TRH-DA throughout the study period.
- T3 treatment led to a significant decrease in pancreatic TRH concentrations from day 3 onwards.
- T3 treatment had minimal impact on TRH-DA, with a notable increase only observed on day 28.
Conclusions:
- Thyroid hormones exert differential effects on pancreatic TRH and TRH-DA.
- Evidence suggests a direct action of thyroid hormones on pancreatic TRH and an inductive effect on TRH-DA.
- Pancreatic TRH-DA may play a crucial role in fine-tuning TRH concentrations during neonatal development.
Abstract:
High concentrations of thyrotrophin-releasing hormone (TRH) in the rat pancreas were detected during the first few days of life decreasing thereafter while pancreatic TRH-degrading activity (TRH-DA) absent at birth appeared on day 14 and increased to reach adult values by day 21. This period of life is also remarkable by the low level of circulating thyroid hormones. Since TRH-degrading activity may be thyroid hormone dependent it was of interest to study the effects of thyroid status fluctuations both on TRH-DA and TRH content during the neonatal period. In this study, hypo- and hyperthyroidism were induced by 6-n-propyl-2-thiouracil (PTU) and triiodothyronine (T3) respectively. Pancreatic TRH-DA and TRH concentrations were measured at different ages from birth until day 29, in treated animals and results compared to control age-matched rats. In hypothyroid rats, pancreatic TRH concentrations remained significantly higher after day 16 while TRH-DA was lower during the whole period studied. Following T3 treatment, pancreatic TRH concentrations decreased significantly from day 3 onwards. However, no significant changes were found for TRH-DA except a two-fold increase on day 28. These results suggest that two different mechanisms may account for thyroid hormones action: 1) a direct effect on pancreatic TRH 2) an inductive saturable effect on TRH-DA. Furthermore a fine tuner modulatory role of TRH-DA on TRH concentrations cannot be excluded.
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