Effects of age on the metabolism of thyroid hormones by rat brain tissue in vitro.

Using a newly-devised chromatographic method for the separation of the acetic and propionic analogues of triiodothyronine (T3) and thyroxine (T4), we studied the metabolism of radioactively labeled T3 and T4 in rat brain homogenates to determine whether the rates of metabolism and the types of products formed are influenced by the age of the animal. The separation of metabolites is achieved on silica gel H in a solvent system consisting of methylacetate-2.5% ammonia (W/V) (95:5 V/V). Results clearly demonstrate that the metabolism of both T3 and T4 is age-dependent. Metabolism of T3 occurred at a significant rate during the early postnatal period (11 and 23 days), declined sharply between 23 and 40 days and was almost completely absent in the adult brain (100 days). Free iodide was the only product that could be identified in extracts of the reaction mixture. Neither the acetic nor propionic acid analogues of T3 were present in significant amounts. In the case of T4, iodide was the major metabolite formed. In addition, a significant amount of triiodothyroacetic acid was present in extracts of homogenates from the 11- and 23-day-old rats but not in those from older animals. Although initially, the rate of T4 metabolism was greater in the younger animals, over a 6-hour period, the amount metabolized was approximately the same at all ages studied. We conclude that these age-dependent changes in the metabolism of T3 and T4 may influence T3 receptor interactions in brain tissue and thereby regulate hormonal activity at the cellular level during the critical period of brain development.