Thyroid Hormones Flashcards
What are the chemical names for the thyroid hormones T3 and T4?
T3 is known as triiodothyronine and T4 is thyroxine.
Very briefly describe the structure of the thyroid follicles.
The central luminal region of a thyroid follicle contains colloid that is surrounded by a layer of follicular epithelial cells. Colloid functions to concentrate iodide, produce thyroglobulin as well as T3 and T4.
What is the limiting step of hormone synthesis in normal thyroid? What enzyme is involved in the I pump mechanism? What is the approximate normal thyroid to serum I ratio? What are the effects of CI04 and SCN?
Limiting step in hormone synthesis in normal thyroid is Iodine uptake by the follicular cells. An ouabain-sensitive- Na/K ATPase is believed to be involved in the mechanism of this step. Normally the thyroid concentration of Iodine is 25X that of serum. CI04- is an ion with similar partial specific volume that can inhibit the pump whereas SCN- is a competitive inhibitor of transport that is not stored.
What is iodinated by the reaction involving hydrogen peroxide, iodide ion and thyroid peroxidase?
Oxidation and organification of the Iodine requires H202 thyroid peroxidase. In the presence of I, H202 and thyroid peroxidase can cause iodination of some of the tyrosyl residues on thyroglobulin.
What is the function of thyroglobulin? What is special about its structure? Where is it stored and where is it degraded?
Thyroglobulin is arranged in such a way that it acts as a template to line up iodinated tyrosyl residues sufficiently close to one another and at correct angles so that they can react in order to become coupled. These iodinated forms of thyroglobulin act as pre-prohormone which acts as a storage form of T4, and T4 that is first transported to the lumen where a several weeks supply of prepared of thyroglobulin is stored. It is degraded by lysosomes on the luminal border of the follicular cells while en route to the serosal side of the cell.
What happens to most of the T4 in the target tissues? What is reverse T3?
In target tissue, T4 is deiodinated to yield T3 by the enzyme 5’ deiodinase. Reverse T3 is an inactive form of T3, that is sometimes formed usually in largest amounts in chronic diseases, starvation and in the fetus.
To what proteins are T3 and T4 bound while in the circulation?
Most of the T3 and T4 are bound to thyroxine binding globulin (TBG) or thyroxine binding prcalbumin (TBPA), better known as transthyretin. A substantial amount of T3 and a small amount of T4 is bound to albumin
Where is the thyroid hormone receptor located? To what superfamily of receptors does it belong?
Thyroid hormone receptor is a member of the steroid receptor superfamily and located in the nucleus.
What are the general effects of thyroid hormones?
Effects of thyroid hormones are anabolic for most tissues. They increase the production of DNA, RNA, epidermal growth factor, nerve growth factor and growth hormone synthesis. T3 increases activity of cytochrome oxidase, cytochrome c reductase, glycerol-3-phosphate dehydrogenase, synthesis of Na/K ATPase, synthesis of flavoprotein, increases intestinal absorption of glucose, catecholamine induced release of glucose from liver and increases hepatic degradation of insulin.
What is Goiter?
Enlargement of the thyroid gland due to TSH increases (usually due to iodine deficiency, the thyroid attempts to compensate by increasing its sensitivity to TSH)
What is Grave’s disease?
Hyperactivity of the thyroid due to a thyroid-stimulating antibody that binds to the TSH receptor activating it. It causes sweating, nervousness, insomnia, diarrhea, and exophthalmos.
What is Cretinism?
Neonatal thyroid hormone deficiency that causes retardation of brain maturation and growth.
What is myxedema?
In adults - hypothyroidism - results in slow speech, slow reflexes, poor memory, fatigue, and constipation. Hypothyroidism is treated with thyroxine.
By what mechanism do antithyroid drugs function? What is 131Iodine used for?
Antithyroid drugs such as thiourea derivative thiouracil, propylthiouracil and methimazole inhibit organificaiton of iodine. These compounds and ablation of the thyroid by radioactive 131Iodine can be used to treat hyperthyroidism.
