1. POLYCHLORINATED BIPHENYL EFFECTS ON AVIAN HEPATIC ENZYME INDUCTION AND THYROID FUNCTION Catherine M. Webb and F. M. Anne McNabb Department of Biological Sciences, Virginia Tech Introduction. Polychlorinated biphenyls (PCBs) induce the activity of the hepatic enzyme uridine diphosphate-glucuronosyltransferase (UDP-GT) which glucuronidates the thyroid hormone, thyroxine (T4), in mammals. Glucuronidation increases T4 solubility in water, which leads to its excretion. This enhanced loss of T4 can then lead to hypothyroidism. It is not clear how PCBs affect UDP-GT in birds. Previous bird studies have used a substrate that measures all UDP-GT isozymes so they may not have accurately reflected T4 glucuronidation. I hypothesize that PCBs will induce avian UDP-GT isozymes that glucuronidate T4, increase thyroid gland (TG) weight, decrease TG hormone content, and decrease plasma T4 concentrations. Objectives To develop and validate an assay for measuring avian UDP-GT activity toward T4 To compare UDP-GT induction by PCBs in birds and mammals To study the effects of PCBs on avian thyroid function Experimental Design Conclusions PCBs significantly increased UDP-GT activity in both species but less in quail than mice Quail are less sensitive to Aroclor 1254 than mice Quail showed some thyroid effects but were not hypothyroid; mice were hypothyroid (decreased plasma T4) Unclear whether the HPT axis was activated in quail; activation of HPT axis appears to be inhibited in mice Higher dose of Aroclor 1254 may clarify some differences between birds and mammals in their responses to PCBs Significance This is the first demonstration of a T4-specific mechanism by which PCBs induce hypothyroidism in birds. Abstract. Environmental exposure to polychlorinated biphenyls (PCBs; common, persistent environmental contaminants) has been associated with histological evidence of thyroid deficiency in wild birds. PCBs decrease thyroid function in mammals by inducing a liver enzyme, uridine diphosphate-glucuronosyltransferase (UDP- GT). This enzyme adds carbohydrate to PCBs, thereby facilitating their excretion from the body. UDP-GT has the same effect on the predominant thyroid hormone, thyroxine (T4) and this increased excretion of T4 can lead to thyroid deficiency (hypothyroidism). Our objective was to determine if PCBs affected UDP-GT and thyroid function in birds as is the case in mammals. We validated an assay for measuring UDP-GT activity toward T4 in Japanese quail, and then UDP-GT induction by Aroclor 1254 (common PCB mixture) was evaluated in quail and mice. In Experiment 1, quail and mice were dosed orally with solvent or Aroclor 1254 (250 or 500 mg/kg) and sacrificed 5 days later. In Experiment 2, Japanese quail were dosed orally with solvent or Aroclor 1254 (500 mg/kg) and sacrificed 5 or 21 days later. Total liver UDP-GT capacity increased with Aroclor 1254 exposure in all treatment groups of both species, but the effect was smaller in quail than in mice. Enzyme induction led to a trend to decreased plasma T4 concentrations at both doses and exposure times in quail and significantly decreased plasma T4 concentrations at both doses in mice. PCBs altered thyroid function in quail, but they did not become hypothyroid. This was in contrast to mice, which did become hypothyroid. Overall, quail showed a lesser response than mice to equivalent doses of Aroclor 1254, so it appears that birds may be less vulnerable to PCBs than mammals. Supported by a Virginia Tech Graduate Research Development grant. Results Figure 1. Effects of Aroclor 1254 on Balb/c mice (Experiment 1): a) UDP-GT activity (pmol T4G per mg liver per min); b) UDP-GT capacity (pmol T4G per g body wt per min); c) liver weight; d) plasma T4 concentrations; e) plasma T3 concentrations. Each value represents the mean ± SE of 5 mice. Asterisks indicate significant differences from controls (*p < 0.05; **p < 0.01). Figure 2. Effects of Aroclor 1254 on Japanese quail (Experiment 2): a) UDP-GT activity (pmol T4G per mg liver per min); b) UDP-GT capacity (pmol T4G per g body wt per min); c) liver weight; d) plasma T4 concentrations; e) plasma T3 concentrations. Each value represents the mean ± SE of 11-13 quail. Asterisks indicate significant differences from controls (*p < 0.05; **p < 0.01). Experiment 1Experiment 2 Animals 12-day-old Japanese quail, weanling mice 12-day-old Japanese quail Oral dose of Aroclor 1254 (mg/kg) 0 (vegetable oil), 250, 500 0 (vegetable oil), 500 Day of sacrifice 5 days5 or 21 days Tissues collected Blood, livers, thyroid glands Endpoints measured Body weight, thyroid gland weight, liver weight, UDP-GT activity toward T4, plasma T4 and T3 concentrations, thyroid gland T4 and T3 content