Neonatal hyperthyroidism alters hepatic epidermal growth factor receptor ontogeny in mice
Related Experiment Videos
1Department of Pediatrics, Karolinska Institute, St. Goran's Children's Hospital, Stockholm, Sweden.
Abstract:
Epidermal growth factor (EGF) liver receptor ontogeny and somatic growth were studied in mice from day 7 to day 70 postnatally to assess long-term effects of short-term postnatal thyroxine treatment. The mice were given 0.4 micrograms thyroxine/g body weight/day for the 1st wk of life. EGF receptor binding in liver tissue was studied on days 7, 15, 20, 30, and 70 postnatally. Treated animals had accelerated eyelid opening and tooth eruption, and permanent growth retardation was obvious from the second week of life. Hepatic EGF receptor-binding capacity increased markedly in control mice with increasing age in contrast to a very slow increase in treated mice, making the difference statistically significant (P less than 0.01) from day 30. The affinity of EGF receptor binding initially was similar in the two groups of animals (1.09 x 10(9) M-1 and 1.02 x 10(9) M-1) and increased by day 30 in controls (2.57 x 10(9) M-1), an increase that was not observed in treated animals either at day 30 or 70. These results suggest a sensitive period of imprinting during the first 7 days postnatally, a period when thyroxine can exert a permanent effect on later growth and later hepatic EGF receptor number.
Insights
Early postnatal thyroxine treatment in mice permanently stunts growth and impairs liver epidermal growth factor (EGF) receptor development. This highlights a critical developmental window for thyroxine
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Thyroid hormones play a crucial role in mammalian development and growth.
- Epidermal Growth Factor (EGF) signaling is vital for liver development and function.
- Postnatal development involves complex interactions between hormones and growth factors.
Purpose of the Study:
- To investigate the long-term effects of short-term postnatal thyroxine administration on somatic growth and hepatic EGF receptor ontogeny in mice.
- To determine if there is a sensitive period during early postnatal life when thyroxine can permanently alter growth and EGF receptor dynamics.
Main Methods:
- Mice received thyroxine (0.4 µg/g body weight/day) during the first postnatal week.
- EGF receptor binding in liver tissue was assessed at multiple time points (days 7, 15, 20, 30, and 70).
- Somatic growth parameters, including eyelid opening and tooth eruption, were monitored.
Main Results:
- Postnatal thyroxine treatment led to accelerated eyelid opening and tooth eruption, followed by permanent growth retardation.
- Hepatic EGF receptor-binding capacity showed a significantly slower increase in treated mice compared to controls from day 30 onwards (P < 0.01).
- The affinity of EGF receptor binding increased in controls by day 30 but remained unchanged in thyroxine-treated animals.
Conclusions:
- A sensitive imprinting period exists within the first postnatal week where thyroxine can induce permanent alterations in growth.
- Early thyroxine exposure permanently affects the ontogeny of hepatic EGF receptor number and binding affinity.
- These findings underscore the critical role of thyroid hormones during early development for establishing long-term physiological regulation.