Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism.

Abstract

As bstract. Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 1251-T4, '25I-T3(T4), and 13'I-T3 were measured at various times after injecting '251-T4 and 13'I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In euthyroid rats, fractional turnover rates of T3 per hour were: Cx, 0.26±0.02 (SE); Cm, 0.20±0.02; L, 0.98±0.07; R, 0.97±0.12; and the calculated unidirectional plasma T3 clearance by these tissues were, in milliliters per gram per hour: Cx = 0.38, Cm = 0.32, L = 5.0, and R = 5.6. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While >80% May 24, 1984. of the '25I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 1251. T3(T4) were 2.7-and 1.5-fold greater than in euthyroid rats. In the Cx, this response resulted from an approximately sixfold increase in fractional conversion and an approximately fourfold decrease in T3 removal rate hampered by a decreased uptake of T4 from plasma, whereas in Cm the response resulted only from the reduced T3 removal rate. In euthyroid rats, the calculated production rate of T3 in nanograms per gram per hour by the Cx was 0.96 and 0.89 by the Cm, which on a per organ basis equals 15 and 2%, respectively, of the extrathyroidal production rate as assessed in the body pool exchanging with plasma. Several conclusions can be drawn: (a) Production of T3 by developing brain is a very active process in agreement with the need of thyroid hormones during this period. (b) The brainplasma exchange of T3 is slow compared with that of L or R. (c) This, along with the active local production, explains the predominant role of the latter as a source of T3 for the brain. (d) In hypothyroidism, the Cx is protected by an increase in the efficiency of T4 to T3 conversion and a prolonged residence time of T3 in the tissue, whereas the Cm is protected only by the latter. Because of the large fraction of the tissue T3 produced locally and the active turnover rate of T3 in the brain, reductions in T3 removal rate are of utmost importance for T3 homeostasis in these tissues.

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

“…In the pituitary, the rise in TSH during hypothyroxinemia (such as in the early stage of Hashimoto's thyroiditis or during iodine deficiency) is a typical example of the extreme sensitivity of the hypothalamic-pituitary thyroid axis which anticipates a problem with thyroid hormone supply by monitoring the concentration of T4. In the hypothyroid condition, D3-mediated inactivation of T3 and T4 is reduced, helping to compensate for the reduction of T4 (28,29).…”

Cognitive effects of endocrine-disrupting chemicals in animals.

“…Infants exposed to higher levels of PCBs and dioxins had lower free T 4 levels and higher thyroid-stimulating hormone levels. Thyroid hormone is transported to the brain as T 4 and then converted locally to T 3 (67). Based on this knowledge, it has been argued that the dramatic reductions in serum T 4 reported in rats after perinatal PCB exposure could place the brain at special risk for hypothyroid-related effects (68) (64) found that, although both serum and brain T 4 levels were reduced after fetal PCB exposure, brain T 3 levels remained normal or near normal.…”

Novel translational repressor (NAT-1) expression is modified by thyroid state and age in brain and liver

“…2). The levels start to decline after 48 h. This is a very rapid response considering that TH equilibration in cerebral tissue requires at least 3 h (25). At the present time, it is not known if TH increases the transcription rate of this gene or stabilizes the mRNA, or both.…”

“…Thyroxine rather than T 3 was used in the time course experiments because the transport of thyroxine to the brain is more efficient than that of T 3 (26), and up to 80% of T 3 in the brain arises locally from thyroxine (25).…”