TSH Regulates the Function of the Thyroid Gland

Thyroid Factor

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The thyroid gland is composed of aggregates of follicles, which are formed from a single layer of cells. The follicular cells produce and secrete thyroxine (T4) and triiodothyronine (T3), thyroid hormones that are iodinated derivatives of the amino acid tyrosine. The thyroid hormones act on many cells by changing the expression of certain genes, changing the capacity of their target cells to produce particular proteins. These changes are thought to bring about the important actions of the thyroid hormones on the differentiation of the CNS, on body growth, and on the pathways of energy and intermediary metabolism.

Thyroid-stimulating hormone (TSH) is the physiological regulator of T4 and T3 synthesis and secretion by the thyroid gland. It also promotes nucleic acid and protein synthesis in the cells of the thyroid follicles, maintaining their size and functional integrity. The actions of TSH on thyroid hormone synthesis and secretion, and the physiological effects of the thyroid hormones, are described in detail in Chapter 33.

The Structure and Synthesis of TSH. TSH is a glyco-protein consisting of two structurally different subunits. The a subunit of human TSH is a single peptide chain of 92 amino acid residues with two carbohydrate chains linked to its structure. The P subunit is a single peptide chain of 112 amino acid residues, to which a single carbohydrate chain is linked. The a and P subunits are held together by noncovalent bonds. The two subunits combined give the TSH molecule a molecular weight of about 28,000.

Neither subunit has significant TSH activity by itself. The two subunits must be combined in a 1:1 ratio to form an active hormone. The gonadotropins FSH and LH are also composed of two noncovalently combined subunits. The a subunits of TSH, FSH, and LH are derived from the same gene and are identical, but the P subunit gives each hormone its particular set of physiological activities.

Thyrotrophs synthesize the peptide chains of the a and P subunits of TSH from separate mRNA molecules, which are transcribed from two different genes. The peptide chains of the a and P subunits are combined and undergo glycosylation in the rough ER. These processes are completed as TSH molecules pass through the Golgi apparatus and are packaged into secretory granules. Normally, thyrotrophs make more a subunits than P subunits. As a result, secretory granules contain excess a subunits. When a thy-rotroph is stimulated to secrete TSH, it releases both TSH and free a subunits into the bloodstream. In contrast, very little free TSH P subunit is in the blood.

TRH and TSH Synthesis and Secretion. Thyrotropin-re-leasing hormone (TRH) is the main physiological stimulator of TSH secretion and synthesis by thyrotrophs. TRH is a small peptide consisting of three amino acid residues produced by neurons in the hypothalamus. These neurons terminate on the capillary networks that give rise to the hy-pophyseal portal vessels. Normally, these neurons secrete TRH into the hypophyseal portal circulation at a constant or tonic rate. It is assumed that the TRH concentration in the blood that perfuses the thyrotrophs does not change greatly,- therefore, the thyrotrophs are continuously exposed to TRH.

TRH binds to receptors on the plasma membranes of thyrotrophs. These receptors are coupled to PLC by G proteins (Fig. 32.8). The interaction of TRH with its receptor activates PLC, causing the hydrolysis of PIP2 in the membrane. This action releases the intracellular messengers IP3 and DAG. IP3 causes the concentration of Ca2+ in the cytosol to rise, which stimulates the secretion of TSH into the blood.



Trh Ca2 Dag

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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