Principles of Biochemistry Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Hormones
Thyroid hormones regulate the metabolic rate

The Thyroid Gland secretes two characteristic Hormones: L-thyroxine and L-triiodothyronine (Fig. 25-24). Like adrenaline, these two hormones, abbreviated as T4 and T3 respectively, are Tyrosine derivatives. THYROID HORMONES are produced in response to signals sent to the Hypothalamus, which secretes thyrotropin-releasing hormone as well as a thyroid-stimulating hormone release-inhibiting factor. Thyrotropin-releasing hormone stimulates the release of thyrotropin from the anterior Pituitary Gland into the bloodstream. Thyrotropin binds to specific receptors on thyroid Cells and stimulates their production of thyroid hormones. Thyroxine and triiodothyronine are synthesized through a sequence of enzymatic reactions beginning with the iodination of L-tyrosine residues in thyroglobulin (a glycoprotein with a Molecular Weight of 650,000), which converts them into L-monoiodotyrosine residues (Fig. 25-24). Iodine, which is an essential trace element required for this reaction (Chapter 26), is delivered to the thyroid gland via the Blood. Iodine is intensively bound and accumulated by thyroglobulin, also known as the colloid protein, and is subsequently used to iodinate the tyrosine residues within thyroglobulin. In the subsequent stages of thyroid hormone synthesis, the iodotyrosine residues remain attached to thyroglobulin. Almost all newly formed thyroxine and triiodothyronine remain bound to thyroglobulin in the thyroid follicles until they are released into the blood through the action of Proteolytic Enzymes. It is believed that thyroxine serves as a precursor, or prohormone, for triiodothyronine, which stimulates METABOLISM.

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Fig. 25-24. Thyroid hormones (A and B) and monoiodotyrosine (C)—the first iodinated precursor of thyroid hormones.

Next, thyroid hormones are carried by the bloodstream to target Organs. Thyroid hormones exert a stimulating effect on the majority of Tissues, with notable exceptions being the adult Brain and certain reproductive tissues. The metabolism of The Liver and Muscles is stimulated particularly strongly by thyroid hormones. They bind to specific receptor Proteins, which in turn facilitate The entry of thyroxine into the Cell Nucleus. As a result of the interaction between thyroxine-receptor complexes and specific genes in target cells, the synthesis of certain enzymes and enzyme systems increases sharply. The primary outcome of thyroid hormone action is an increase in the basal metabolic rate of the animal.

The basal metabolic rate (BMR) is a measure of an Organism's oxygen consumption under conditions of complete rest, 12 hours after a meal, calculated per unit of body surface area. A patient's BMR is expressed as a percentage deviation from the normal BMR value—that is, the percentage deviation from the norm for individuals of the same sex, weight, and height. BMR measurements are performed in the Diagnosis of thyroid disorders. The condition caused by elevated thyroid hormone secretion is called hyperthyroidism. In this state, the basal metabolic rate is increased, food is burned faster than normal, patients dissipate more heat, and they exhibit increased excitability. Conversely, a deficiency in thyroid hormone secretion, or hypothyroidism, is manifested by a lowered basal metabolic rate. Patients with hypothyroidism are characterized by slower-than-normal metabolic combustion of food, lower heat production, and a certain generalized sluggishness. Dietary iodine deficiency leads to goiter (Chapter 26), which is accompanied by a marked enlargement of the thyroid gland due to the accumulation of a much larger amount of colloid protein than normal, produced in an effort to capture the minimal amounts of iodine circulating in the blood.

The question of how thyroid hormones regulate The rate of aerobic metabolism remains a mystery despite numerous studies in this area. Specifically, it remains unclear how thyroid hormones influence The activity of Mitochondria, where the processes of Respiration and ATP generation predominantly take place. Thyroid hormones are also capable of accelerating the maturation and development of certain tissues; for example, they stimulate the metamorphosis of a tadpole into an adult frog.