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Corticosterone hypersecretion in preweanling rats exposed neonatally to trimethyltin
M E Stanton1, M E Coussons, C M Kuhn
1Neurotoxicology Division (MD-74B), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Insights
Neonatal exposure to trimethyltin (TMT) alters the stress hormone corticosterone (CS) response in developing rats. This effect varies based on the timing of TMT exposure and the age at which the stress response is measured.
Area of Science:
- Endocrinology
- Neurotoxicology
- Developmental Biology
Background:
- Developmental neurotoxicity is a growing concern.
- Endocrine disruption can significantly impact neurodevelopment.
- Organotins are environmental contaminants with known neurotoxic effects.
Purpose of the Study:
- To investigate the impact of developmental trimethyltin (TMT) exposure on the corticosterone (CS) stress response in rat pups.
- To determine if the timing of TMT exposure influences the subsequent CS response to stress.
- To examine the age-dependent effects of TMT exposure on endocrine function.
Main Methods:
- Long-Evans rat pups were exposed to TMT (6 mg/kg) or vehicle via intraperitoneal injection on postnatal days 5 or 10.
- Pups were subjected to restraint stress and maternal deprivation.
- Plasma corticosterone levels were measured at various time points (postnatal days 12, 16, and 20) after stress exposure.
Main Results:
- Developmental TMT exposure increased corticosterone (CS) secretion in response to stress.
- TMT exposure on postnatal day 5 led to elevated CS on postnatal days 12 and 16, but not 20.
- TMT exposure on postnatal day 10 resulted in elevated CS on postnatal days 16 and 20.
- Exposure on postnatal day 15 also caused CS hypersecretion when tested on postnatal day 20.
Conclusions:
- Neonatal exposure to TMT alters the corticosterone stress response in a manner dependent on the age of exposure and the age of testing.
- These findings highlight the sensitivity of the developing endocrine system to environmental toxicants like organotins.
- Developmental TMT exposure can lead to persistent alterations in stress hormone regulation.
Abstract:
Developmental neurotoxicity may be influenced by effects of a compound on endocrine function. Here we report that developmental exposure to TMT increases the corticosterone (CS) response to stress in developing rat pups. Long-Evans rat pups were injected i.p. with either 6 mg/kg TMT hydroxide (in 10 microliters/g BW NaCl) or vehicle on Postnatal Day 5 (PND5) or 10 and were then tested for their CS response to restraint stress on PND12, 16, or 20. In the stress test, pups were maternally deprived in individual compartments of an incubator for 24 hr, and then blood sampled by decapitation either immediately (basal), or 30, 60 or 90 min after the onset of a 15-min period of restraint in a wire-mesh holder. Regardless of TMT exposure or age of testing, this procedure produced a peak in plasma CS at 30 min which then recovered to basal levels by 90 min. TMT exposure on PND5 (Experiment 1) resulted in CS hypersecretion relative to vehicle-injected controls on PND12 and 16 but not PND20. TMT exposure on PND10 (Experiment 2) had no effect at PND12 but elevated CS over vehicle controls at PND16 and 20. PND15 exposure to TMT resulted in CS hypersecretion in pups tested on PND20. Neonatal organotin exposure appears to alter CS secretion in a manner that is influenced by age of exposure and age of testing.