Brain and Cerebrospinal Fluid Permeability to Intravenous Thyroid Hormones*

Abstract

Labeled thyroxine (T4) and triiodothyronine (T3) given by constant intravenous infusion to dogs for 4 hr penetrate both brain and cerebrospinal fluid (CSF). Labeled T4 reached a steady state distribution between serum, CSF, and cerebral cortex tissue water (CCTW). Labeled T3 entered CCTW more readily than T4 but was slower to reach steady state distribution in CSF. Distribution ratios ofendogenous, nonlabeled T3 and T4 between serum, CSF, and CCTW compartments were similar. The more ready brain penetration of T3 is probably due to a less ionized state at pH 7.4 than T4. Failure of labeled albumin to penetrate CSF during the experimental period suggested a greaterpermeability to free than protein-bound hormone. Impaired transport of labeled free T4 into CSF under conditions of T4 loading was consistent with a carrier mechanism with a transport maximum. Comparison of the influx rates of protein-bound hormones to the efflux of T4 and T3 revealed an imbalance theoretically correctable onlyby influx of free hormone. The presence of higher free hormone levels iri CSF than serum presents a concentration gradient that may be related to difference in amount of binding protein orcould result from an active transport mechanism for T3and T4 influx. Thus the evidence is consistent with entry of T3 and T4 into the CNS as free hormones via a carriermediated transport mechanism; further studies would require control ofthe hormone content of physiologic fluids on both sides of the transport mechanism. (Endocrinology95: 1398, 1974)