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Essential role for polyamine biosynthesis in thyroxine stimulated pancreatic development in neonatal rats
1Department of Pediatrics, Wayne State University, Detroit, MI.
Insights
Thyroxine accelerates pancreatic development in rat pups by increasing ornithine decarboxylase (ODC) and polyamines. Inhibiting ODC with DFMO suppressed these thyroxine-induced pancreatic growth effects.
Area of Science:
- Endocrinology
- Developmental Biology
- Biochemistry
Background:
- Thyroxine administration accelerates pancreatic maturation in neonatal rats.
- Ornithine decarboxylase (ODC) and polyamines are crucial for cell growth and differentiation.
Purpose of the Study:
- To investigate the role of ODC and polyamines in thyroxine-induced precocious pancreatic development in rat pups.
- To determine if ODC inhibition affects thyroxine-mediated pancreatic maturation.
Main Methods:
- Neonatal rat pups received daily thyroxine injections.
- Pancreatic ODC activity, polyamine levels, amylase concentration, DNA, and protein were measured over 10 days.
- Difluoromethyl ornithine (DFMO), an ODC inhibitor, was administered to dams to assess its impact on pups.
Main Results:
- Thyroxine induced a biphasic increase in pancreatic ODC activity, peaking on days 2 and 5.
- Increased polyamine concentrations (putrescine, spermidine) correlated with ODC peaks.
- Thyroxine treatment led to significant increases in pancreatic weight, protein, and amylase activity.
- DFMO administration significantly inhibited ODC activity and suppressed thyroxine-induced increases in pancreatic weight, protein, and amylase.
Conclusions:
- Increased ODC activity and polyamine levels are critical mediators of thyroxine-induced precocious pancreatic development.
- ODC plays a key role in mediating the effects of thyroxine on pancreatic maturation.
Abstract:
Administration of thyroxine to rat pups leads to precocious development of the pancreas. The role of ornithine decarboxylase (ODC) and polyamines in thyroxine-induced pancreatic maturation was examined. Rat pups (aged 5 days) were given daily subcutaneous injection of thyroxine (0.1 micrograms/g body wt.) until the day before death. Serial ODC activities were measured in pancreatic homogenates after 1, 2, 3, 4, 5, 6, 7 and 10 days of thyroxine treatment. There was a biphasic induction of ODC activities by thyroxine: an early peak appeared on day 2 of treatment followed by a decrease on day 4; a second peak was evident on day 5 and then a decrease to control values by day 7. Significant increases in tissue concentrations of putrescine and spermidine were observed concomitant with two peaks of ODC activity. Pancreatic amylase concentration, DNA and protein also showed a significant increase after thyroxine treatment. Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, given orally (8% in drinking water) to nursing dams at postnatal day 5 for 5 days caused an 83% inhibition of pancreatic ODC activity in thyroxine-treated pups when compared to thyroxine-treated pups not exposed to DFMO. Concomitantly, the thyroxine-induced increases in pancreatic weight, protein and amylase activity were suppressed. Our results suggest that increases in ODC activities and polyamine levels are critical intermediary steps in the precocious induction of pancreatic development by thyroxine.