Hypothyroidism and abnormalities in the kinetics of thyroid hormone metabolism in rats treated chronically with polychlorinated biphenyl and polybrominated biphenyl.

Abstract

Studies were directed at the question of whether polychlorinated biphenyl (PCB; Aroclor 1254) and polybrominated biphenyl (PBB; Fire Master BP-6), when administered in the diets of female Sprague-Dawley rats over long periods of time (5-7 months) and at low dosages (0, 1, 5, 10, and 50 ppm), would depress the thyroid. By examining serum T3 and T4, kinetics of T4 metabolism, and in vivo thyroid response to exogenous TSH injections, an estimate of the degree of hypothyroidism was made, and abnormalities in T4 disappearance from serum were encountered. Serum T3 and T4 levels were greatly suppressed in a dose-related manner by PCB or PBB treatment. There was a diminished response of serum T3 and T4 to TSH injection in rats pretreated with PCB or PBB (5 and 10 ppm), the exception being T3 in the 5 ppm PCB treatment group. Had the PCB and PBB treatment-induced suppression of T4 and T3 been on the hypothalamo-pituitary axis, the response of the treated rats to exogenous TSH might have exceeded that of controls; however, the opposite occurred. Disappearance of injected doses of L-[125I]T4 diminished as treatment concentrations of PCB or PBB increased. Disappearance slopes (r = 0.98) and fractional turnover rate constants (k) were decreased (t1/2 was lengthened) at each treatment level compared to the control values. The T4 distribution space (per 100 g BW) was expanded with increasing dosage by as much as 8-fold in the 50 pmm PCB treatment group. T4 MCRs were not increased by PCB or PBB treatment; thus, decreases in serum T3 and T4 were not caused by increased catabolism. T4 production rates were decreased at all treatment levels, but maximally 6-fold by 50 ppm PCB treatment. Together these data indicate that PCB-PBB-induced decreases in serum T3 and T4 result primarily from direct damage to the thyroid rather than any enhanced hepatic or other peripheral catabolism per se. Expanded T4 distribution space demonstrated that nonthyroid damage was also an important factor in reducing serum T4. Cell membrane damage associated with PCB-PBB intoxication may have expanded pools for T4 dilution. The findings are consistent with reported histological and ultrastructural damage caused by PCB and PBB. It also appears that TSH plays little role in PCB-PBB-induced hypothyroidism.