Maintenance of homeostasis

For an organism to function normally and effectively, it is necessary that the biochemical processes of its tissues operate smoothly and conjointly in a stable setting. The endocrine system provides an essential mechanism called homeostasis that integrates body activities and at the same time ensures that the composition of the body fluids bathing the constituent cells remains constant.

Scientists have postulated that the concentrations of the various salts present in the fluids of the body closely resemble the concentrations of salts in the primordial seas, which nourished the simple organisms from which increasingly complex species have evolved. Any change in the salt composition of fluids that surround cells, such as the extracellular fluid and the fluid portion of the circulating blood (the serum), necessitates large compensating changes in the salt concentrations within cells. As a result, the constancy of these salts (electrolytes) inside and outside of cells is closely guarded. Even small changes in the serum concentrations of these electrolytes (e.g., sodium, potassium, chloride, calcium, magnesium, and phosphate) elicit prompt responses from the endocrine system in order to restore normal concentrations. These responses are initiated through negative feedback regulatory mechanisms similar to those described above.

Not only is the concentration of each individual electrolyte maintained through homeostasis, but the total concentration of all of the electrolytes per unit of fluid (osmolality) is maintained as well. If this were not the case, an increase in extracellular osmolality (an increase in the concentrations of electrolytes outside of cells) would result in the movement of intracellular fluid across the cell membrane into the extracellular fluid. Because the kidneys would excrete much of the fluid from the expanded extracellular volume, dehydration would occur. Conversely, decreased serum osmolality (a decrease in the concentrations of electrolytes outside of cells) would lead to a buildup of fluid within the cells.

Another homeostatic mechanism involves the maintenance of plasma volume. If the total volume of fluid within the circulation increases (overhydration), the pressure against the walls of the blood vessels and the heart increases, stimulating sensitive areas in heart and vessel walls to release hormones. These hormones, called natriuretic hormones, increase the excretion of water and electrolytes by the kidney, thus reducing the plasma volume to normal.

Hormonal systems also provide for the homeostasis of nutrients and fuels that are needed for body metabolism. For example, the blood glucose concentration is closely regulated by several hormones to ensure that glucose is available when needed and stored when in abundance. After food is ingested, increased blood glucose concentrations stimulate the secretion of insulin. Insulin then stimulates the uptake of glucose by muscle tissue and adipose tissue and inhibits the production of glucose by the liver. In contrast, during fasting, blood glucose concentrations and insulin secretion decrease, thereby increasing glucose production by the liver and decreasing glucose uptake by muscle tissue and adipose tissue and preventing greater reductions in blood glucose concentrations.

Male muscle, man flexing arm, bicep curl.
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Growth and differentiation

Despite the many mechanisms designed to maintain a constant internal environment, the organism itself is subject to change: it is born, it matures, and it ages. These changes are accompanied by many changes in the composition of body fluids and tissues. For example, the serum phosphate concentration in healthy children ranges from about 4 to 7 mg per 100 ml (1.1 to 2.1 millimole per litre [mmol/l]), whereas the concentration in normal adults ranges from about 3 to 4.5 mg per 100 ml (1 to 1.3 mmol/l). These and other more striking changes are part of a second major function of the endocrine system—namely, the control of growth and development. The mammalian fetus develops in the uterus of the mother in a system known as the fetoplacental unit. In this system the fetus is under the powerful influence of hormones from its own endocrine glands and hormones produced by the mother and the placenta. Maternal endocrine glands assure that a proper mixture of nutrients is transferred by way of the placenta to the growing fetus. Hormones also are present in the mother’s milk and are transferred to the suckling young.

Sexual differentiation of the fetus into a male or a female is also controlled by delicately timed hormonal changes. Following birth and a period of steady growth in infancy and childhood, the changes associated with puberty and adolescence take place. This dramatic transformation of an adolescent into a physically mature adult is also initiated and controlled by the endocrine system. In addition, the process of aging and senescence in adults is associated with endocrine-related changes.

Adaptive responses to stress

Throughout life the endocrine system and the hormones it secretes enhance the ability of the body to respond to stressful internal and external stimuli. The endocrine system allows not only the individual organism but also the species to survive. Acutely threatened animals and humans respond to stress with multiple physical changes, including endocrine changes, that prepare them to react or retreat. This process is known as the “fight-or-flight” response. Endocrine changes associated with this response include increased secretion of cortisol by the adrenal cortex, increased secretion of glucagon by the islet cells of the pancreas, and increased secretion of epinephrine and norepinephrine by the adrenal medulla.

Adaptive responses to more prolonged stresses also occur. For example, in states of starvation or malnutrition, there is reduced production of thyroid hormone, leading to a lower metabolic rate. A low metabolic rate reduces the rate of the consumption of the body’s fuel and thus reduces the rate of consumption of the remaining energy stores. This change has obvious survival value since death from starvation is deferred. Malnutrition also causes a decrease in the production of gonadotropins and sex steroids, reducing the need for fuel to support reproductive processes.

Parenting behaviour

The endocrine system, particularly the hypothalamus, the anterior pituitary, and the gonads, is intimately involved in reproductive behaviour by providing physical, visual, and olfactory (pheromonal) signals that arouse the sexual interest of males and the sexual receptivity of females. Furthermore, there are powerful endocrine influences on parental behaviour in all species, including humans.

Integrative functions

The endocrine systems of humans and other animals serve an essential integrative function. Inevitably, humans are beset by a variety of insults, such as trauma, infection, tumour formation, genetic defects, and emotional damage. The endocrine glands play a key role in mediating and ameliorating the effects of these insults on the body. Subtle changes in the body’s fluids, although less obvious, also have important effects on storage and expenditure of energy and steady and timely growth and development. These subtle changes largely result from the constant monitoring and measured response of the endocrine system.

The menstrual cycle in women and the reproductive process in men and women are under endocrine control. The endocrine system works in concert with the nervous system and the immune system. When functioning properly, these three systems direct the orderly progression of human life and protect and defend against threats to health and survival.

Synthesis and transport of hormones

Hormone synthesis

Endocrine cells are rather homogeneous in appearance and are usually cuboidal in shape. When viewed under an electron microscope (a microscope of extraordinary magnifying power), the fine, detailed structure of endocrine cells can be seen. Many of the various intracellular structures, called organelles, are involved in the sequence of events that occurs during the synthesis and secretion of hormones. In the case of protein hormone synthesis, the target cell is stimulated when a hormone or other substance binds to a receptor on the surface of the cell. For example, growth hormone-releasing hormone binds to receptors on the surface of anterior pituitary cells to stimulate the synthesis and secretion of growth hormone.

In some cases, protein hormone synthesis can be stimulated by the entrance of a metabolite into the cytoplasm or nucleus of a target cell. This type of stimulation occurs when glucose enters insulin-producing beta cells in the islets of Langerhans of the pancreas. There are also hormones and metabolites that lead to the inhibition of specific cellular activities. For example, dopamine is released from neurons and binds to receptors on lactotrophs in the anterior pituitary to inhibit the secretion of prolactin.

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The stimulation of a receptor at the cell surface is followed by a series of complex events within the cell membrane. Events that occur within the cell membrane then stimulate activities within the cell that lead to the activation of specific genes in the nucleus. Genes contain unique sequences of DNA that code for specific protein hormones or for enzymes that direct the synthesis of other hormones. The transcription of genes results in the formation of messenger ribonucleic acid (mRNA) molecules.

In the case of hormone stimulation, the mRNA molecules contain the translated code required for synthesis of the target protein hormone (or enzyme). When mRNA leaves the nucleus and associates with the endoplasmic reticulum in the cytoplasm, it directs the synthesis of a relatively inert precursor to the hormone, called a prohormone, from amino acids available within the cytoplasm. The prohormone is then transported to an organelle called the Golgi apparatus, where it is packaged into vesicles known as secretory granules. As the granules migrate to the cell surface the prohormone is cleaved by a special enzyme called a proteolytic enzyme that separates the inactive region from the active region of the hormone. Through a process known as exocytosis, the active hormone is discharged through the cell wall into the extracellular fluid. It should be noted that the same signal that increases the synthesis of a protein hormone usually also increases the immediate release of hormone from already synthesized secretory granules into the extracellular fluid.

The precursor of all steroid hormones, cholesterol, is produced in nonendocrine tissues (e.g., the liver) or is obtained from the diet. The cholesterol is then taken up by the adrenal gland and the gonads and is stored in vesicles within the cytoplasm. Through the actions of several enzymes, cholesterol is converted into steroid hormones.

The first step in steroid hormone synthesis is the conversion of cholesterol into pregnenolone, which occurs in mitochondria (organelles that produce most of the energy used for cellular processes). This conversion is mediated by a cleavage enzyme, the synthesis of which is stimulated in the adrenal glands by corticotropin (adrenocorticotropin, or ACTH) or angiotensin and in the ovaries and testes by follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Adrenocorticotropin, angiotensin, follicle-stimulating hormone, and luteinizing hormone also stimulate the production of enzymes required for later steps in steroid hormone synthesis. Once pregnenolone is formed, it is transported out of the mitochondria and into the endoplasmic reticulum, where it undergoes further enzymatic conversion to progesterone. Progesterone is then converted into specific steroid hormones. For example, in the ovaries and testes, progesterone is converted into androgens and estrogens, and in the adrenal cortex, progesterone is converted into androgens, mineralocorticoids, which regulate salt and water metabolism, and glucocorticoids, which stimulate the breakdown of fat and muscle to metabolites that can be converted to glucose in the liver.

The process of thyroid hormone synthesis is mediated by several enzymes. The synthesis of these enzymes is stimulated by the anterior pituitary hormone thyrotropin (thyroid-stimulating hormone, or TSH). Thyroid hormone synthesis is unique in that it requires iodine, which is available only from the diet, and it occurs within an already synthesized protein known as thyroglobulin. Thyroglobulin also serves as a storage protein and must be broken down to release thyroid hormone.