Thermoregulatory deficits in adult Long Evans rat exposed perinatally to the antithyroidal drug, propylthiouracil

摘要

Developmental exposure to endocrine disrupting drugs and environmental toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic pituitary thyroid (HPT) axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known antithyroidal properties. PTU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10ppm from gestational day (GD) 6 through postnatal day (PND) 21. Adult male offspring were implanted with radiotransmitters to monitor Tc and motor activity (MA) and were observed undisturbed at an ambient temperature of 22°C for 12 consecutive days. Data were averaged into a single 24hour period to minimize impact of ultradian changes in Tc and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10ppm PTU exhibited a marked deviation in their regulated Tc with a reduction of approximately 0.4°C below that of controls throughout the daytime period and a smaller reduction at night. Rats exposed to 1 or 2ppm also had smaller but significant reductions in Tc. MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in Tc of adult offspring that was independent of changes in MA.