第37章内分泌系

The basal metabolic rate, which is the amount of calories required by the body at rest, is determined by two hormones produced by the thyroid gland: thyroxine, also known as tetraiodothyronine or T₄, and triiodothyronine, also known as T₃. These hormones affect nearly every cell in the body except for the adult brain, uterus, testes, blood cells, and spleen. They are transported across the plasma membrane of target cells and bind to receptors on the mitochondria resulting in increased ATP production. In the nucleus, T₃ and T₄ activate genes involved in energy production and glucose oxidation. This results in increased rates of metabolism and body heat production, which is known as the hormone’s calorigenic effect.

T₃ and T₄ release from the thyroid gland is stimulated by thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary. TSH binding at the receptors of the follicle of the thyroid triggers the production of T₃ and T₄ from a glycoprotein called thyroglobulin. Thyroglobulin is present in the follicles of the thyroid, and is converted into thyroid hormones with the addition of iodine. Iodine is formed from iodide ions that are actively transported into the thyroid follicle from the bloodstream. A peroxidase enzyme then attaches the iodine to the tyrosine amino acid found in thyroglobulin. T₃ has three iodine ions attached, while T₄ has four iodine ions attached. T₃ and T₄ are then released into the bloodstream, with T₄ being released in much greater amounts than T₃. As T₃ is more active than T₄ and is responsible for most of the effects of thyroid hormones, tissues of the body convert T₄ to T₃ by the removal of an iodine ion. Most of the released T₃ and T₄ becomes attached to transport proteins in the bloodstream and is unable to cross the plasma membrane of cells. These protein-bound molecules are only released when blood levels of the unattached hormone begin to decline. In this way, a week’s worth of reserve hormone is maintained in the blood. Increased T₃ and T₄ levels in the blood inhibit the release of TSH, which results in lower T₃ and T₄ release from the thyroid.

The follicular cells of the thyroid require iodides (anions of iodine) in order to synthesize T₃ and T₄. Iodides obtained from the diet are actively transported into follicle cells resulting in a concentration that is approximately 30 times higher than in blood. The typical diet in North America provides more iodine than required due to the addition of iodide to table salt. Inadequate iodine intake, which occurs in many developing countries, results in an inability to synthesize T₃ and T₄ hormones. The thyroid gland enlarges in a condition called goiter, which is caused by overproduction of TSH without the formation of thyroid hormone. Thyroglobulin is contained in a fluid called colloid, and TSH stimulation results in higher levels of colloid accumulation in the thyroid. In the absence of iodine, this is not converted to thyroid hormone, and colloid begins to accumulate more and more in the thyroid gland, leading to goiter.

Disorders can arise from both the underproduction and overproduction of thyroid hormones. Hypothyroidism, underproduction of the thyroid hormones, can cause a low metabolic rate leading to weight gain, sensitivity to cold, and reduced mental activity, among other symptoms. In children, hypothyroidism can cause cretinism, which can lead to intellectual disabilities and growth defects. Hyperthyroidism, the overproduction of thyroid hormones, can lead to an increased metabolic rate and its effects: weight loss, excess heat production, sweating, and an increased heart rate. Graves’ disease is one example of a hyperthyroid condition.

Regulation of blood calcium concentrations is important for generation of muscle contractions and nerve impulses, which are electrically stimulated. If calcium levels get too high, membrane permeability to sodium decreases and membranes become less responsive. If calcium levels get too low, membrane permeability to sodium increases and convulsions or muscle spasms can result.

Blood calcium levels are regulated by parathyroid hormone (PTH), which is produced by the parathyroid glands, as illustrated in Figure 37.12. PTH is released in response to low blood Ca²⁺ levels. PTH increases Ca²⁺ levels by targeting the skeleton, the kidneys, and the intestine. In the skeleton, PTH stimulates osteoclasts, which causes bone to be reabsorbed, releasing Ca²⁺ from bone into the blood. PTH also inhibits osteoblasts, reducing Ca²⁺ deposition in bone. In the intestines, PTH increases dietary Ca²⁺ absorption, and in the kidneys, PTH stimulates reabsorption of the Ca²⁺. While PTH acts directly on the kidneys to increase Ca²⁺ reabsorption, its effects on the intestine are indirect. PTH triggers the formation of calcitriol, an active form of vitamin D, which acts on the intestines to increase absorption of dietary calcium. PTH release is inhibited by rising blood calcium levels.

Hyperparathyroidism results from an overproduction of parathyroid hormone. This results in excessive calcium being removed from bones and introduced into blood circulation, producing structural weakness of the bones, which can lead to deformation and fractures, plus nervous system impairment due to high blood calcium levels. Hypoparathyroidism, the underproduction of PTH, results in extremely low levels of blood calcium, which causes impaired muscle function and may result in tetany (severe sustained muscle contraction).

The hormone calcitonin, which is produced by the parafollicular or C cells of the thyroid, has the opposite effect on blood calcium levels as does PTH. Calcitonin decreases blood calcium levels by inhibiting osteoclasts, stimulating osteoblasts, and stimulating calcium excretion by the kidneys. This results in calcium being added to the bones to promote structural integrity. Calcitonin is most important in children (when it stimulates bone growth), during pregnancy (when it reduces bone loss), and during prolonged starvation (because it reduces bone mass loss). In healthy nonpregnant, unstarved adults, the role of calcitonin is unclear.