The thyroid follicles secrete thyroxine, also called tetraiodothy-ronine (T4), in response to stimulation by thyroid-stimulating hormone (TSH) from the anterior pituitary (chapter 11; see fig. 11.23). The thyroid also secretes smaller amounts of tri-iodothyronine (T3) in response to stimulation by TSH. Almost all organs in the body are targets of thyroxine action. Thyroxine itself, however, is not the active form of the hormone within the target cells; thyroxine is a prehormone that must first be converted to triiodothyronine (T3) within the target cells to be active (chapter 11). Acting via its conversion to T3, thyroxine (1) regulates the rate of cell respiration and (2) contributes to proper growth and development, particularly during early childhood.
Thyroxine (via its conversion to T3) stimulates the rate of cell respiration in almost all cells in the body—an effect believed to be due to a lowering of cellular ATP concentrations. This effect is produced by (1) the production of uncoupling proteins (as in brown fat, discussed previously); and (2) stimulation of active transport Na+/K+pumps, which serve as an energy sink to further lower ATP concentrations. As discussed in chapter 4, ATP exerts
Glucocorticoids (e.g., cortisol)
fatty CoA acid acids acids J J
Ketone Glucose bodies
Blood f Free t Ketone t Glucose f Amino fatty bodies acids acids
■ Figure 19.15 The metabolic effects of glucocorticoids. The catabolic actions of glucocorticoids help to raise the blood concentration of glucose and other energy-carrier molecules.
an end-product inhibition of cell respiration, so that when ATP concentrations decrease, the rate of cell respiration increases.
Much of the energy liberated during cell respiration escapes as heat, and uncoupling proteins increase the proportion of food energy that escapes as heat. Since thyroxine stimulates the production of uncoupling proteins and the rate of cell respiration, the actions of thyroxine increase the production of metabolic heat. The heat-producing, or calorigenic (calor = heat) effects of thyroxine are required for cold adaptation.
The metabolic rate under carefully defined resting conditions is known as the basal metabolic rate (BMR). This rate of basal metabolism has two components—one that is independent of thyroxine action and one that is regulated by thyroxine. In this way, thyroxine acts to "set" the BMR. The BMR can thus be used as an index of thyroid function. Indeed, such measurements were used clinically to evaluate the condition of the thyroid prior to the development of direct chemical determinations of T4 and T3 in the blood. A person who is hypothyroid may have a basal O2 consumption about 30% lower than normal, while a person who is hyperthyroid may have a basal O2 consumption up to 50% higher than normal.
A normal level of thyroxine secretion is required for growth and proper development of the central nervous system in children. This is why hypothyroidism in children can cause cretinism (see fig. 11.27). The symptoms of hypothyroidism and hyperthyroidism in adults are compared in table 11.8, p. 311.
A normal level of thyroxine secretion is required in order to maintain a balance of anabolism and catabolism. For reasons that are incompletely understood, both hypothyroidism and hyperthyroidism cause protein breakdown and muscle wasting.
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