An analysis of the interrelationship of nuclear and plasma triiodothyronine in the sea lamprey, lake trout, and rat: evolutionary considerations.

We have studied the interrelationship of plasma and hepatic nuclear T3 in two lower vertebrates, lake trout and sea lamprey. Specific nuclear T3-binding sites were observed in liver of both species. Binding affinities for T3 and several analogs in lamprey and trout were similar to those in rat liver. The findings of identical sedimentation coefficients, Stokes radii, and mol wt suggest a high degree of homology of the receptor molecule among these species. In lamprey ammocoete, both total (approximately 26 nM) and free (approximately 0.12 nM) T3 concentrations were 7- to 36-fold higher than in the trout or rat. The concentration of free T4 was 4 times greater than that in rat plasma despite somewhat lower total T4 levels. This resulted from a 6 times lesser binding of T4 by ammocoete plasma. Total and free T3 and T4 levels fell sharply during transformation to the adult form. In trout, a 27 times greater concentration of free T3 in hepatic nuclei than in cytosol, previously documented for rat liver, gave evidence of the early evolution of an active transport process between these compartments. Analysis of [125I]T3 interchange in trout indicated the existence of two kinetically distinct compartments within the liver, an outer compartment in rapid equilibrium with plasma, and a slowly equilibrating compartment decaying with a t1/2 of 3.7 h. T3 associated with the nuclear receptor appeared to be in equilibrium with the slower hepatic compartment. Despite the apparent resemblance of T3 receptors in these species to those in the rat, administration of T3 (200 micrograms/100 g BW for 4 days) to trout caused no increase in hepatic oxygen consumption or the activities of malic enzyme or alpha-glycerophosphate dehydrogenase. Further, such treatment produced no consistent changes in hepatic mRNA activity profiles analyzed by two-dimensional electrophoresis of in vitro translational products. As suggested by the high free T3 concentration in the larval lamprey ammocoete, T3 in early vertebrates may have a primarily developmental function, manifested over a restricted time frame.