Juárez de Ku L M, Sharma-Stokkermans M, Meserve L A
Department of Biological Sciences, Bowling Green State University, OH 43403-0212.
Toxicology. 1994 Nov-Dec;94(1-3):19-30. doi: 10.1016/0300-483x(94)90025-6.
Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism (depressed thyroid hormones). Neonatal rats made hypothyroid by other means (chemical or surgical) have subnormal activity of choline acetyltransferase (ChAT), which catalyzes synthesis of acetylcholine, in the hippocampus and basal forebrain. The present study examined whether neonatal rats with PCB-induced hypothyroidism had depressed ChAT activity in these two brain areas, and whether alterations in ChAT activity were secondary to hypothyroidism rather than/in addition to a direct effect of PCB. Neonatal rats were exposed to PCB by feeding pregnant female rats chow containing various concentrations of PCB (0, 62.5, 125 or 250 ppm) throughout pregnancy and lactation. During postnatal days 4-14, neonatal rats exposed to the highest concentration of PCB were injected with either saline, triiodothyronine (T3), or thyroxine (T4), or were not injected at all. Circulating thyroid hormone levels (T4 and T3) and brain ChAT activity were determined at 15 days of age. All concentrations of PCB depressed circulating T4 levels and ChAT activity in a dose-response manner, but did not modify T3 levels. Injections of T4, but not T3, elevated ChAT activity in PCB-exposed rats to near control levels. Thus, altered ChAT activity in PCB-exposed rats may partially result from the hypothyroidism accompanying PCB poisoning. The possible molecular mechanism(s) of action of PCB on brain ChAT activity remains unclear.
新生大鼠暴露于有毒化学物质多氯联苯（PCB）会引发甲状腺功能减退（甲状腺激素水平降低）。通过其他方式（化学或手术）导致甲状腺功能减退的新生大鼠，其海马体和基底前脑胆碱乙酰转移酶（ChAT，催化乙酰胆碱合成）的活性低于正常水平。本研究调查了因PCB导致甲状腺功能减退的新生大鼠在这两个脑区的ChAT活性是否降低，以及ChAT活性的改变是继发于甲状腺功能减退，还是PCB的直接作用所致，抑或是两者兼而有之。在整个怀孕和哺乳期，通过给怀孕的雌性大鼠喂食含有不同浓度PCB（0、62.5、125或250 ppm）的食物，使新生大鼠暴露于PCB。在出生后第4至14天，给暴露于最高浓度PCB的新生大鼠注射生理盐水、三碘甲状腺原氨酸（T3）或甲状腺素（T4），或者不进行注射。在15日龄时测定循环甲状腺激素水平（T4和T3）以及脑ChAT活性。所有浓度的PCB均以剂量反应方式降低循环T4水平和ChAT活性，但未改变T3水平。注射T4而非T3可使暴露于PCB的大鼠的ChAT活性升高至接近对照水平。因此，暴露于PCB的大鼠ChAT活性改变可能部分是由PCB中毒伴随的甲状腺功能减退所致。PCB对脑ChAT活性的可能分子作用机制仍不清楚。
