甲状腺激素的合成【拓展用】.pptVIP

Cells of the developing brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development.[26] A transport protein that seems to be important for T4 transport across the blood-brain barrier (OATP1C1) has been identified.[27] A second transport protein (MCT8) is important for T3 transport across brain cell membranes.[27] Non-genomic actions of T4 are those that are not initiated by liganding of the hormone to intranuclear thyroid receptor. These may begin at the plasma membrane or within cytoplasm. Plasma membrane-initiated actions begin at a receptor on the integrin alphaV beta3 that activates ERK1/2. This binding culminates in local membrane actions on ion transport systems such as the Na(+)/H(+) exchanger or complex cellular events including cell proliferation. These integrins are concentrated on cells of the vasculature and on some types of tumor cells, which in part explains the proangiogenic effects of iodothyronines and proliferative actions of 第二十八页，共30页。 thyroid hormone on some cancers including gliomas. T4 also acts on the mitochondrial genome via imported isoforms of nuclear thyroid receptors to affect several mitochondrial transcription factors. Regulation of actin polymerization by T4 is critical to cell migration in neurons and glial cells and is important to brain development.T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin alpha V beta3. In the blood, T4 and T3 are partially bound to thyroxine-binding globulin (TBG), transthyretin, and albumin. Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity. As with the steroid hormones and retinoic acid, thyroid hormones cross the cell membrane and bind to intracellular receptors (α1, α2, β1 and β2), which act alone, in pairs or together with the retinoid X-recepto