MAHER, R.D.*; GRASMAN, K.A.; FOX, G.A.; MCNABB, F.M.A.; Virginia Tech, Blacksburg; Wright State, Dayton, OH; Environment Canada, Hull; Virginia Tech, Blacksburg: Polychlorinated Biphenyl (PCB) Inhibition of Thyroid Hormone (TH) Transport in Plasma Deposition into Oocytes

Environmental PCBs are persistent contaminants that disrupt thyroid function in some mammals. Part of this disruption may result from displacement of T4 from the transport binding protein, transthyretin (TTR). This displacement should increase the percent of free-T4 (FT4) thereby altering T4 metabolism, excretion and entry into cells. If PCBs alter thyroid hormone (TH) binding in birds, such disruptions could alter the circulating free and bound TH concentrations in embryos by decreasing maternal TH deposition into eggs. We addressed PCB effects on plasma T4 binding and egg T4 deposition in herring gull samples collected between 1998 and 2001 from the Great Lakes and a reference site (25-30 fold range in yolk-sac sum-PCBs). Our studies of prefledgling and adult gull plasma samples suggest that environmental PCBs are increasing FT4 concentrations and decreasing plasma T4 binding capacity (presumably by displacing T4 from TTR). Our measurements on whole egg homogenates show a trend toward lower THs in eggs from high PCB sites than those from the reference site. Together these results suggest that PCBs are displacing hormone binding to plasma proteins, increasing free hormone concentrations and thereby increasing hormone excretion. This interpretation is consistent with other studies in our laboratory suggesting trends toward hypothyroidism in gulls from high PCB sites. Our current work is focusing on the use of electrophoretic studies to determine the relative binding affinities of different TH-binding proteins for T4 to assess how these relationships are altered by PCBs. Supported by EPA grant #R-827400-01-0 to FMAM and TSRI grant #301 to GAF and USEPA GR825216-01-0 & Lake Erie Protection Fund 97-37 to KAG.