title: Thermoregulatory deficits in adult Long Evans rat exposed perinatally to the antithyroidal drug, propylthiouracil.
abstract: 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 (T(c)) 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 10 ppm 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 24 hour period to minimize impact of ultradian changes in T(c) and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10 ppm PTU exhibited a marked deviation in their regulated T(c) 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 2 ppm also had smaller but significant reductions in T(c). MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in T(c) of adult offspring that was independent of changes in MA.
authors.affiliation: Toxicology Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: johnstone.andrew@epa.gov.
authors.forename: Andrew F M
authors.initials: AF
authors.lastname: Johnstone
authors.forename: Mary E
authors.initials: ME
authors.lastname: Gilbert
authors.forename: Cenk
authors.initials: C
authors.lastname: Aydin
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Grace
authors.forename: Masashi
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gordon
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008991:Monitoring, Physiologic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D011441:Propylthiouracil / Q000633:toxicity*; D051381:Rats; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D014284:Triiodothyronine; D011441:Propylthiouracil; D013972:Thyrotropin; D013974:Thyroxine
keywords: Core body temperature; Developmental exposure; GD; Gestational day; HPT; Homeostasis; Hypothalamic pituitary thyroid axis; Hypothyroidism; MA; Motor activity; PND; PTU; Parts-per-million; Postnatal day; Propylthiouracil; Propylthiouracil (PTU); Tc; Telemetry; Thermoregulation; ppm