Hormones

Chapter 29


Hormones



A hormone is a chemical substance produced in the body by an organ, cells of an organ, or scattered cells, having a specific regulatory effect on the activity of an organ or organs.15 Hormones are produced at one site in the body and exert their action(s) at distant sites through what is called the endocrine system. It is increasingly recognized that many hormones exert actions locally through what is termed the paracrine system. Finally, some hormones exert their action on the cells of origin, regulating their own synthesis and secretion via an autocrine system. The classic endocrine hormones include insulin, thyroxine, and cortisol. Neurotransmitters and neurohormones are examples of the paracrine system, and certain growth factors that stimulate synthesis and secretion of true hormones from the same cell are examples of an autocrine system.


Table 29-1 lists hormones that are commonly measured in clinical practice plus a few others to illustrate concepts. Biochemical, clinical, and analytical information for specific hormones may be found in Chapters 26 and 46 through 57.




Classification


Hormones are classified as (1) polypeptides or proteins, (2) steroids, or (3) derivatives of amino acids.






Release and Action of Hormones


The physiologic functions of hormones have been broadly categorized into those that (1) affect growth and development, (2) exert homeostatic control of metabolic pathways, and (3) regulate the production, use, and storage of energy. The descriptions that follow illustrate examples of these functions and mechanisms of control of hormone secretion.



Growth and Development


Normal growth and development of the whole human organism is dependent on the complex integrative function of many hormones, including gonadal steroids (estrogen and androgen), growth hormone, cortisol, and thyroxine. Several pituitary hormones are responsible specifically for the growth and development of endocrine glands themselves, and thus are responsible for control of synthesis and secretion of other hormones. Those other hormones can provide negative feedback on secretion of the pituitary hormones. Other regulators of secretion of the pituitary hormones include circadian rhythms and a hypothalamic pulse generator that controls the pulsatile secretion of gonadotropins. Examples of hormones of the anterior pituitary gland include the following:




Homeostatic Control of Metabolic Pathways


The metabolic pathways under hormonal control are diverse and complex. The following important examples illustrate the feedback control of hormone secretion, which is critical for homeostasis:



• Regulation of blood glucose: In response to a glucose load, insulin is promptly released from the pancreas, which regulates the dispersal of glucose into cells (fat, muscle, liver, and brain) for the metabolism necessary to produce energy from glucose (see Chapter 26). As circulating glucose concentrations thus return to preload concentrations, insulin secretion slows. Several counter-regulatory hormones come into play to further regulate this process to ensure that blood glucose concentrations do not become too low. These include glucagon, cortisol, epinephrine, and growth hormone. Recent attention has focused on a group of gastrointestinal hormones termed incretins (see Chapter 46) that are released during eating and stimulate insulin secretion from the pancreas in advance of any measurable increase in blood glucose. Incretins also affect the rate of absorption of nutrients from the gut by slowing down the rate of gastric emptying. Another mechanism by which incretins have a role in the regulation of blood glucose is by delaying release of the counter-regulatory hormone glucagon from the alpha cells of the pancreatic islets. The most studied incretins are glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP).


• Regulation of serum calcium (see Chapter 52): The calcium-sensing receptor (CaSR) on the parathyroid gland recognizes the ambient concentration of ionized calcium, which in turn regulates the synthesis and secretion of PTH. When ionized calcium concentrations fall (so imperceptibly that most analytical methods could not detect the change), PTH synthesis and secretion are stimulated. This additional PTH will attempt to restore serum ionized calcium by enhancing renal tubular reabsorption of calcium and calcium efflux from the skeleton. PTH also catalyzes the synthesis of the renal hormone calcitriol (1,25-dihyroxycholecalciferol), which acts on the gut to increase intestinal absorption of calcium. These very rapid responses of PTH and calcitriol quickly restore ionized calcium to concentrations where the CaSR is no longer activated, and PTH and calcitriol synthesis and secretion return to basal rates.


• Water and electrolyte metabolism is regulated by aldosterone from the adrenal gland, renin from the kidney, and vasopressin [antidiuretic hormone (ADH)] from the posterior pituitary gland (see Chapters 48, 53, and 54).



Regulation of the Production, Use, and Storage of Energy


Under normal conditions, regulation of energy production, use, and storage is under tight hormonal control. Under conditions of changing demands that require more energy (e.g., exercise, starvation, infection or trauma, emotional stress), many hormones are upregulated to control not only circulating levels of nutrients but also the metabolism of these nutrients into necessary energy. This very complex activity, which may involve hormones from different organs, as already alluded to in the preceding section, is under neurologic control, with numerous neuroendocrine hormones participating actively in this integrative metabolic process, which affects most organs in the body and modulates, for example, heart rate, sweating, fertility, and reproduction.



Role of Hormone Receptors


The “unique” or specific action of a hormone on its target tissue is a function of the interaction between the hormone and its receptor. As discussed previously, several types of hormone-receptor interactions may occur.3,5,8,17 The hormone-receptor complex provides the very high specificity of the action of the hormone, allowing the target tissue to accumulate the hormone from among all the molecules to which it is exposed. This is essential because hormones generally circulate in picomolar or nanomolar concentrations (10−9 to 10−12 mol/L).


Hormone receptors may be on the cell surface or may be intracellular within the cytoplasm or nucleus.



Cell-Surface Receptors


Peptide hormones bind to cell surface receptors, and the conformational change resulting from this binding activates an effector system, which in turn is responsible for the downstream actions of the hormone (Figure 29-1).11,12 For most peptide hormones, the intracellular effector that is activated by the hormone-receptor interaction is a specific G-protein (guanyl-nucleotide–binding protein),4,10,13,18 and the receptors are called G-protein–coupled receptors (GPCRs; Figure 29-2). GPCRs are hepta-helical molecules with seven membrane-spanning domains. The amino terminus is extracellular, and the carboxy terminus is intracellular. The major structural classes of GPCRs have been identified, each containing receptors for specific subsets of hormones (Figure 29-3). Group I is the largest group, containing receptors for many peptide hormones and catecholamines. Group II contains receptors for the family of gastrointestinal hormones (secretin, glucagons, and vasoactive intestinal polypeptide). Group III contains the CaSR and the glutamate receptor. Stimulation of a G-protein initiates the intracellular processes of signal transduction that characterize the specific action of the hormone. G-proteins are composed of α, β, and γ subunits and are classified according to the α subunit, of which 20 have been identified to date (see Figure 29-3). G-proteins may stimulate adenylate cyclase (GS type of G-proteins) or may inhibit adenylate cyclase (Gi type). The many classes of GPCRs and G-proteins briefly described in this section provide some insight into the mechanisms responsible for the specificity of hormone action. Some nonpeptide hormones also use cell surface receptors.


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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Hormones

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