7 18.3 Regulation of Body Processes

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 mental retardation 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 18.12. 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.

Hormonal Regulation of Growth

Hormonal regulation is required for the growth and replication of most cells in the body. Growth hormone (GH), produced by the anterior portion of the pituitary gland, accelerates the rate of protein synthesis, particularly in skeletal muscle and bones. Growth hormone has direct and indirect mechanisms of action. The first direct action of GH is stimulation of triglyceride breakdown (lipolysis) and release into the blood by adipocytes. This results in a switch by most tissues from utilizing glucose as an energy source to utilizing fatty acids. This process is called a glucose-sparing effect. In another direct mechanism, GH stimulates glycogen breakdown in the liver; the glycogen is then released into the blood as glucose. Blood glucose levels increase as most tissues are utilizing fatty acids instead of glucose for their energy needs. The GH mediated increase in blood glucose levels is called a diabetogenic effect because it is similar to the high blood glucose levels seen in diabetes mellitus.

The indirect mechanism of GH action is mediated by insulin-like growth factors (IGFs) or somatomedins, which are a family of growth-promoting proteins produced by the liver, which stimulates tissue growth. IGFs stimulate the uptake of amino acids from the blood, allowing the formation of new proteins, particularly in skeletal muscle cells, cartilage cells, and other target cells, as shown in Figure 18.13. This is especially important after a meal, when glucose and amino acid concentration levels are high in the blood. GH levels are regulated by two hormones produced by the hypothalamus. GH release is stimulated by growth hormone-releasing hormone (GHRH) and is inhibited by growth hormone-inhibiting hormone (GHIH), also called somatostatin.

A balanced production of growth hormone is critical for proper development. Underproduction of GH in adults does not appear to cause any abnormalities, but in children it can result in pituitary dwarfism, in which growth is reduced. Pituitary dwarfism is characterized by symmetric body formation. In some cases, individuals are under 30 inches in height. Oversecretion of growth hormone can lead to gigantism in children, causing excessive growth. In some documented cases, individuals can reach heights of over eight feet. In adults, excessive GH can lead to acromegaly, a condition in which there is enlargement of bones in the face, hands, and feet that are still capable of growth.

Hormonal Regulation of Stress

When a threat or danger is perceived, the body responds by releasing hormones that will ready it for the “fight-or-flight” response. The effects of this response are familiar to anyone who has been in a stressful situation: increased heart rate, dry mouth, and hair standing up.

Fight-or-Flight Response

Interactions of the endocrine hormones have evolved to ensure the body’s internal environment remains stable. Stressors are stimuli that disrupt homeostasis. The sympathetic division of the vertebrate autonomic nervous system has evolved the fight-or-flight response to counter stress-induced disruptions of homeostasis. In the initial alarm phase, the sympathetic nervous system stimulates an increase in energy levels through increased blood glucose levels. This prepares the body for physical activity that may be required to respond to stress: to either fight for survival or to flee from danger.

However, some stresses, such as illness or injury, can last for a long time. Glycogen reserves, which provide energy in the short-term response to stress, are exhausted after several hours and cannot meet long-term energy needs. If glycogen reserves were the only energy source available, neural functioning could not be maintained once the reserves became depleted due to the nervous system’s high requirement for glucose. In this situation, the body has evolved a response to counter long-term stress through the actions of the glucocorticoids, which ensure that long-term energy requirements can be met. The glucocorticoids mobilize lipid and protein reserves, stimulate gluconeogenesis, conserve glucose for use by neural tissue, and stimulate the conservation of salts and water. The mechanisms to maintain homeostasis that are described here are those observed in the human body. However, the fight-or-flight response exists in some form in all vertebrates.

The sympathetic nervous system regulates the stress response via the hypothalamus. Stressful stimuli cause the hypothalamus to signal the adrenal medulla (which mediates short-term stress responses) via nerve impulses, and the adrenal cortex, which mediates long-term stress responses, via the hormone adrenocorticotropic hormone (ACTH), which is produced by the anterior pituitary.

Short-term Stress Response

When presented with a stressful situation, the body responds by calling for the release of hormones that provide a burst of energy. The hormones epinephrine (also known as adrenaline) and norepinephrine (also known as noradrenaline) are released by the adrenal medulla. How do these hormones provide a burst of energy? Epinephrine and norepinephrine increase blood glucose levels by stimulating the liver and skeletal muscles to break down glycogen and by stimulating glucose release by liver cells. Additionally, these hormones increase oxygen availability to cells by increasing the heart rate and dilating the bronchioles. The hormones also prioritize body function by increasing blood supply to essential organs such as the heart, brain, and skeletal muscles, while restricting blood flow to organs not in immediate need, such as the skin, digestive system, and kidneys. Epinephrine and norepinephrine are collectively called catecholamines.

Concept in Action

Watch this

Discovery Channel animation describing the flight-or-flight response.

Long-term stress response differs from short-term stress response. The body cannot sustain the bursts of energy mediated by epinephrine and norepinephrine for long times. Instead, other hormones come into play. In a long-term stress response, the hypothalamus triggers the release of ACTH from the anterior pituitary gland. The adrenal cortex is stimulated by ACTH to release steroid hormones called corticosteroids. Corticosteroids turn on transcription of certain genes in the nuclei of target cells. They change enzyme concentrations in the cytoplasm and affect cellular metabolism. There are two main corticosteroids: glucocorticoids such as cortisol, and mineralocorticoids such as aldosterone. These hormones target the breakdown of fat into fatty acids in the adipose tissue. The fatty acids are released into the bloodstream for other tissues to use for ATP production. The glucocorticoids primarily affect glucose metabolism by stimulating glucose synthesis. Glucocorticoids also have anti-inflammatory properties through inhibition of the immune system. For example, cortisone is used as an anti-inflammatory medication; however, it cannot be used long term as it increases susceptibility to disease due to its immune-suppressing effects.

Mineralocorticoids function to regulate ion and water balance of the body. The hormone aldosterone stimulates the reabsorption of water and sodium ions in the kidney, which results in increased blood pressure and volume.

Hypersecretion of glucocorticoids can cause a condition known as Cushing’s disease, characterized by a shifting of fat storage areas of the body. This can cause the accumulation of adipose tissue in the face and neck, and excessive glucose in the blood. Hyposecretion of the corticosteroids can cause Addison’s disease, which may result in bronzing of the skin, hypoglycemia, and low electrolyte levels in the blood.

Summary