By Alan Balsam, M.D.
The Thorndike Laboratory of Harvard Medical School and the Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02115
ABSTRACT. Studies were performed of the peripheral metabolism of radioiodine-labeled T3 and rT3 in the rat. Two methods of analysis were employed to determine the residual concentrations of labeled hormones after their single iv injection: trichloroacetic acid-ethanol extraction, as employed by others, and a recently described technique for the chromatography of plasma on columns of Sephadex G-25. In the case of both T3 and rT3, Sephadex chromatography regularly revealed the appearance in plasma of labeled iodoprotein, radioiodide, and a peak of unidentified radioiodinated materials that eluted just before T3 (pre-T3). Radioiodine in the pre-T3 zone, whether generated from T3 or rT3, proved to be almost completely TCA-precipitable and ethanol extractable. Consequently, for both T3 and rT3, plasma disappearance curves derived by the precipitation-extraction technique were at all time points higher than were curves representing chromatographically isolated administered hormone. In the case of rT3, and to a lesser extent T3, this discrepancy was further accentuated by the inclusion in the precipitable-extractable counts of a significant fraction (about 5%) of the very large proportion of inorganic radioiodine that appeared in the plasma soon after administration of labeled hormone.
As would be expected, metabolic clearance rates of the two hormones calculated by a multicompartmental technique were much higher when based on data generated chromatographically than when based on data obtained by the precipitation-extraction technique. For T3, values of the metabolic clearance rates were 17.7 and 14.9 ml/100 g BW/h, respectively. For 1T3, corresponding values were 250 and 171 ml/100 g BW/h. The more rapid clearance of rT3 than of T3 from plasma could not be explained by less intense binding of the rT3 to plasma proteins; on the contrary, the percentage of free rT3 in rat plasma was found to be only half that of free T3. It is inferred, therefore, that the difference resides in the ability of one or more tissues to take up and degrade rT3 more rapidly than T3. (Endocrinology 102: 1247, 1978)