Hypothyroidism nuclear receptors

Levothyroxine (T4 ) Activation of nuclear receptors results in gene expression with RNA formation and protein synthesis Hypothyroidism See Table 38-1 maximum effect seen after 6-8 weeks of therapy Toxicity See Table 38-4 for symptoms of thyroid excess... 

Observations from our laboratory show that post-infarcted myocardium is more tolerant to ischemia and reperfusion injury. Increased postischemic recovery of function and decreased LDH release were found in perfused rat hearts after 8 weeks of an acute myocardial infarction. This response was associated with downregulation of TRal and TRpi thyroid hormone nuclear receptors. Thus, it is likely that tissue hypothyroidism (at the receptor level) might account for the increased tolerance of those hearts to ischemia and reperfusion injury.215 See also chapter 2. 

In adult rats hypothyroidism does not appear to change the binding properties of the hepatic nuclear recetors [38-39] contrary to what is observed in the brain. The effect of thyroid hormone deficiency on brain nuclear receptors is not uniform in the anterior pituitary the Ka of the receptors increases [25,40] and their number decreases [25]. In the cerebral cortex however the affinity is significantly diminished [25,41] and the number of receptors increased [25,29,41,42]. The observations point to different regulatory mechanisms acting on thyroid hormone receptors in liver and brain, and within different areas of the brain. 

B. Dozin and Ph. De Nayer. Nuclear receptors and cytosolic binding sites for triiodothyronine in rat brain and liver during maturation. Effects of neonatal hypothyroidism, Neuropeptides and Psychosomatic Processes", Endroczi et al., eds.. The Hungarian Academy of Sciences, Budapest (1982). 

The adult brain is endowed with nuclear as well as cytosolic and membrane T3 receptors that have been visualized by autoradiography and studied biochemically [30-33]. Both neurons and neuropil are labeled by [ 1251]T3, and the labeling is selective across brain regions. Functionally, one of the most prominent features of neural action of thyroid hormone in adulthood is subsensitivity to norepinephrine as a result of a hypothyroid state [27], These changes may be reflections of loss of dendritic spines in at least some neurons of the adultbrain. Clinically, thyroid hormone deficiency increases the probability of depressive illness, whereas thyroid excess increases the probability of mania (Ch. 52) in susceptible individuals [27],... 

S. Hamada and Y. Yoshimasa. Increases in brain nuclear triiodothyronine receptors associated with increased triiodothyronine in hyperthyroid and hypothyroid rats. Endocrinology 112 207-211 (1983). 

K. Ishiguro, Y. Suzuki and T. Sato. Effect of neonatal hypothyroidism on maturation of nuclear triiodothyronine (T3) receptors in developing rat brain. Acta Endocrinol. 95 495-499 (1980). 

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