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Hormonal Regulation of Exercise

HORMONAL REGULATION OF EXERCISE The Endocrine System
This system includes all tissues or glands that secrete hormones. • Endocrine glands secrete their hormones directly into the blood. • Hormones act as chemical signals throughout the body. • Specific hormone secreted by the specialized endocrine cells & transported via the blood to specific target cells. Upon reaching their destinations, they can control the activity of the target tissue. • Some hormones affect many body tissues, whereas others target specific cells of the body.

The Nature of Hormones
• Hormones are involved in most physiological processes, so their actions are relevant to many aspects of exercise & sport performance. 1. Steroid Hormones Chemical structure similar to cholesterol & most are derived from it. Lipid soluble & diffuse easily through cell membranes. • E.g. hormones secreted by adrenal cortex (cortisol & aldosterone), ovaries (estrogen & progesterone), testes (testosterone), & placenta (estrogen & progesterone). • • Nonsteroid Hormones Not lipid soluble, so they cannot easily cross cell membranes. Subdivided into 2 groups: protein or peptide hormones & amino acid-derivative hormones. • Hormones from thyroid gland (thyroxine & triiodothyronine) & adrenal medulla (epinephrine & norepinephrine) are amino acid hormones. • All other nonsteroid hormones are protein or peptide hormones. Chemical Classification of Hormones

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2. Hormonal Regulation of Exercise

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Hormone Action

The interaction between the hormone & its specific receptor has been compared to a lock (receptor) & key (hormone) arrangement, in which only the correct key can unlock a given action within the cells. • The combination of hormone bond to its receptor is referred to as a hormonereceptor complex. • Receptors for nonsteroid hormones are located on the cell membrane, whereas receptors for steroid hormones are found either in the cell’s cytoplasm or in its nucleus. • Each hormone is usually specific for a single type of receptor & binds only with its specific receptors, thus affecting only tissues that contain those specific receptors.

The Mechanism of Action of a Steroid Hormones, Leading to direct gene activation • Steroid hormones pass easily through the cell membrane. • Once inside the cell, a steroid hormone binds to its specific receptors. • The hormone-receptor complex then enters the nucleus, binds to part of the cell’s DNA, & activates certain genes. This process is referred to as direct gene activation. • In response to this activation, mRNA is synthesized within the nucleus. • The mRNA then enters the cytoplasm & promotes protein synthesis. These proteins may be:  enzymes that can have numerous effects on cellular processes,  structural proteins to be used for tissue growth & repair, or  regulatory proteins that can alter enzymes function. The Mechanism of Action of a Nonsteroid Hormones, Using a second messenger within the cell • Nonsteroid hormones cannot cross the cell membrane; they react with specific receptors outside the cell, on the cell membrane. • A nonsteroid hormone molecule binds to its receptor and triggers a series of enzymatic reactions that lead to the formation of an intracellular second messenger: cyclic adenosine monophosphate (cyclic AMP, or cAMP). • Attachment of the hormone to membrane receptor activates an enzyme, adenylate cyclase, situated within the cell membrane. This enzyme catalyzes the formation of cAMP from cellular ATP. • cAMP can then produce specific physiological responses, which may include:  activation of cellular enzymes,  change in membrane permeability,  promotion of protein synthesis, or  stimulation of cellular secretions.
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• Thus, nonsteroid hormones typically activate the cAMP system of the cell, which then leads to changes in intracellular functions. 3. Control of Hormone Release Hormone released can be fluctuating over short periods (an hour or less) or over longer periods of time (daily or even monthly cycle: monthly menstrual cycle). • Most hormone secretion is regulated by a negative feedback system. • Secretion of a hormone causes some change in the body, and this change in turn inhibits further hormone secretion. • Negative feedback is the primary mechanism through which the endocrine system maintains homeostasis. • The number of receptors on a cell can be altered to increase or decrease that cell’s sensitivity to a certain hormone. • Up-regulation (sensitization) refers to an increase in receptors, thus the cell becomes more sensitive to that hormone because more can be bound at one time. • Down-regulation (desensitization) refers to a decrease in receptors, thus the cell becomes less sensitive to that hormone because with fewer receptors, less hormone can bind.

SUMMARY
1. 2. Hormones can be classified as either steroid or nonsteroid. Steroid hormones are lipid soluble, and most are formed from cholesterol. Nonsteroid hormones are formed from proteins, or amino acids. Hormones are generally secreted into the blood and then through the body to exert an effect only on their target cells. They act by binding in a lock-and-key manner with specific receptors found only in the target tissues. Steroid hormones pass through cell membranes and bind to receptors inside the cell. They use a mechanism called direct gene activation to cause protein synthesis. Nonsteroid hormones cannot enter the cells easily, so they bind to receptors on the cell membrane. This activates a second messenger within the cell, which in turn can trigger numerous cellular processes. A negative feedback system regulates secretion of most hormones.

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The number of receptors for a specific hormone can be altered to meet the body’s demands. Up-regulation refers to an increase in receptors, and down-regulation is a decrease. These two processes change cell sensitivity to hormones.

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The Endocrine Glands & Their Hormones

The Pituitary Gland (or the Hypophysis) Anterior lobe: Hormone 1: Growth hormone (GH). Target organ: All cells in the body. Major functions: Promotes development & enlargement of all body tissues up through maturation (growth of bone & muscle); increases rate of protein synthesis; increases mobilization of fats and use fat as an energy source; decreases rate of carbohydrate use (sparing glucose).

Hormone 2: Prolactin (PRL). Target organ: Breasts. Major functions: Stimulates breast development & milk secretion (promotes lactation). Hormone 3: Thyrotropin or Thyroid-stimulating hormone (TSH). Target organ: Thyroid gland. Major functions: Controls the amount of thyroxin & triiodothyronine produced & released by the thyroid gland (promotes release of thyroid hormones). Hormone 4: Adrenocorticotropin (ACTH). Target organ: Adrenal cortex. Major functions: Controls the secretion of hormones from the adrenal cortex. Hormone 5: Follicle-stimulating hormone (FSH). Target organ: Ovaries, testes. Major functions: Females - initiates growth & maturation of follicles in the ovaries & promotes secretion of estrogen from the ovaries. Males – promotes development or production of sperm in testes. Hormone 6: Luteinizing hormone (LH). Target organ: Ovaries, testes. Major functions: Females – promotes secretion of estrogen & progesterone and cause the follicle to rupture, releasing the ovum. Males – causes testes to secrete testosterone.
Posterior lobe: Hormone 1: Antidiuretic hormone (ADH or vasopressin).
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Target organ: Kidneys. Major functions: Assists in controlling water excretion by the kidneys; elevates blood pressure by constricting blood vessels. Hormone 2: Oxytocin. Target organ: Uterus, breasts. Major functions: Stimulates contraction of uterine muscles & milk secretion.

Thyroid Gland

Hormone 1: Triiodothyronine (T3) & Thyroxine (T4). Target organ: All cells in the body. Major functions: Increases the rate of cellular metabolism; increases rate & contractility of the heart. Hormone 2: Calcitonin. Target organ: Bones. Major functions: Control calcium ion concentration in the blood.

The parathyroid Gland

Hormone: Parathyroid hormone (PTH/parathormone). Target organ: Bones, intestines, & kidneys. Major functions: Control calcium ion concentration in extracellular fluid through its influence on bones, intestines, and kidneys.

The Adrenal Gland • Medulla Hormone 1: Catecholamine (Epinephrine 0r Adrenaline). Target organ: Most cells in the body. Major functions: Mobilizes glycogen; increases skeletal muscle blood flow; increases heart rate & contractility; oxygen consumption.

Hormone 2: Catecholamine (Norepinephrine or Noradrenaline). Target organ: Most cells in the body. Major functions: Constricts arterioles & venules, thereby elevating blood pressure.
• Cortex
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Hormone 1: Mineralocorticoids (aldosterone). Target organ: Kidneys. Major functions: Increase sodium (NA+) retention & potassium (K+) excretion through the kidneys. Hormone 2: Glucocorticoids (cortisol). Target organ: Most cells in the body. Major functions: Controls metabolism of carbohydrates, fats, & proteins; antiinflammatory action. Hormone 3: Gonadocorticoids (androgens & estrogens). Target organ: Ovaries, breasts, & testes. Major functions: Assists in the development of female & male sex characteristics.

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The Pancreas

Hormone 1: Insulin. Target organ: All cells in the body. Major functions: Controls blood glucose levels by lowering glucose levels; increases use of glucose & synthesis of fat. Hormone 2: Glucagon. Target organ: All cells in the body. Major functions: Increases blood glucose; stimulates the breakdown of fats & proteins. Hormone 3: Somatostatin. Target organ: Islets of Langerhans & gastrointestinal tracts. Major functions: Depresses the secretion of both insulin & glucagons.

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The Gonads

• Testes Hormone: Testosterone. Target organ: Sex organs, muscle. Major functions: Promotes development of male sex characteristics, including growth of testes, scrotum, & penis, facial hair, & change in voice; promotes muscle growth. • Ovaries Hormone: Estrogen & progesterone. Target organ: Sex organs, adipose tissue
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Major functions: Promotes development of female sex organs & characteristics; provides increased storage of fat, assists in regulating the menstrual cycle.

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The Kidneys

Hormone 1: Renin. Target organ: Adrenal cortex. Major functions: Assists in blood pressure control. Hormone 2: Erythropoietin. Target organ: Bone marrow. Major functions: Erythrocyte production.

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Hormonal Effects on Metabolism & Energy
CHO & fat metabolism are responsible for maintaining muscle ATP levels during prolonged exercise. • Various hormones work to ensure glucose & FFA availability for muscle energy metabolism.

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Regulation of Glucose Metabolism During Exercise For the body to meet the energy demands of exercise, more glucose must be available to the muscle. Glucose is stored in the body as glycogen, primarily in the muscles & the liver. Glucose must be freed from storage, so glycogenolysis must increase. So glucose freed from the liver enters the blood to circulate throughout the body. (Glycogenolysis = the conversion of glycogen to glucose) Plasma glucose levels can also be increased through gluconeogenesis. (Gluconeogenesis = the conversion of protein or fat into glucose) Plasma Glucose Level 4 hormones work to increase the amount of plasma glucose (involved in both glycogenolysis & gluconeogenesis) are: glucagon, epinephrine, norepinephrine, & cortisol. At rest, glucose release from the liver is facilitated by glucagon, which promotes liver glycogen breakdown (glycogenolysis) and glucose formation from amino acids (gluconeogenesis). During exercise, glucagon secretion increases.

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Muscular activity also increases the rate of catecholamine release from adrenal medulla, & these hormones (epinephrine & norepinephrine) work with glucagon to further increase glycogenolysis. Cortisol levels also increase during exercise. Cortisol increases protein catabolism, freeing amino acid to be used within the liver for gluconeogenesis. Thus, all 4 of these hormones can increase the amount of plasma glucose by enhancing the processes of glycogenolysis & gluconeogenesis. Glucose Uptake by the muscles Releasing sufficient amounts of glucose into the blood does not ensure that the muscle cells will have enough glucose to meet their energy demands. The glucose must not only be delivered to these cells, it must also be taken up by the muscle cells. This job relies on insulin. Once glucose is delivered to the muscle, insulin facilitates its transport into the muscle fibers. Insulin helps the released glucose enter the muscle cells, where it can be used for energy production. But insulin levels decline during prolonged exercise, indicating that exercise facilitates the action of insulin so that less of the hormone is required during exercise than at rest. Regulation of Fat Metabolism During Exercise During prolonged endurance exercise, CHO reserves become depleted, & the body must rely more heavily on the oxidation of fat for energy production. When CHO reserves are low (low plasma glucose & low muscle glycogen), the endocrine system can accelerate the oxidation of fats (lipolysis) to produce energy. Lipolysis is also enhanced through the elevation of epinephrine & norepinephrine. FFA are stored as triglycerides in fat cells & inside muscle fiber. Adipose tissue triglycerides however must be broken down to release the FFA, which are then transported to the muscle fibers. Triglycerides are reduced to FFA & glycerol by a special enzyme called lipase, which is activated by at least 4 hormones: cortisol; growth hormone; epinephrine, & norepinephrine. Cortisol also accelerates the mobilization & use FFA for energy during exercise. Plasma cortisol levels peak after 30-45 min of exercise then decrease to normal levels. Growth hormone & catecholamine (epinephrine & norepinephrine) continue to activate the mobilization & metabolism of FFA.

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Hormonal Effects on Fluid & Electrolyte Balance During Exercise
• The two primary hormones involved in the regulation of fluid balance are aldosterone & antidiuretic hormone (ADH).
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Aldosterone & the Renin-Angiotensin Mechanism When plasma volume or blood pressure decreases, the kidneys form an enzyme called renin that converts angiotensinogen into angiotensin I, which later becomes angiotensin II. Angiotensin II increases peripheral arterial resistance, raising the blood pressure. Angiotensin II also triggers the release of aldosterone from the adrenal cortex. Aldosterone promotes sodium reabsorption in the kidneys, which in turn causes water retention, thus increasing the plasma volume.

** The influence of water loss from plasma during exercise leads to a sequence of events that promotes sodium (Na+) & water reabsorption from renal tubules, thereby reducing urine production. In the hours after exercise when fluids are consumed, the elevated aldosterone levels cause an increase in the extracellular volume and an expansion of plasma volume. 1. Muscular activity promotes sweating and increases blood pressure. 2. Sweating reduces plasma volume and blood flow to the kidneys. 3. Reduced renal blood flow stimulates rennin release from the kidneys. Renin leads to the formation of angiotensin I, which is converted to angiotensin II. 4. Angiotensin II stimulates the release of aldosterone from the adrenal cortex. 5. Aldosterone increases Na+ and H2O reabsorption from the renal tubules. 6. Plasma volume increases & urine production decreases.

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Antidiuretic Hormone (ADH) ADH is released in response to increased plasma osmolarity (= the ratio of solute to fluid). When osmoreceptors in the hypothalamus sense this increase, the hypothalamus triggers ADH release from the posterior pituitary. ADH acts on the kidneys promoting water conservation. Through this mechanism, the plasma volume is increased, which results in dilution of the plasma solutes. Blood osmolarity decreases.

** The mechanism by which ADH conserves body water. 1. Muscular activity promotes sweating. 2. Sweating causes loss of blood plasma, resulting in hemoconcentration & increased blood osmolarity. 3. Increased blood osmolarity stimulates the hypothalamus.
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4. The hypothalamus stimulates the posterior pituitary gland to secrete ADH. 5. ADH acts on the kidneys, increasing the water permeability of the renal tubules & collecting ducts, leading to increased reabsorption of water. 6. Plasma volume increases, so blood osmolarity decreases after exercise and water ingestion.

SUMMARY
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Plasma glucose is increased by the combined actions of glucagon, epinephrine, norepinephrine, & cortisol. These hormones promote glycogenolysis & gluconeogenesis, thus increasing the amount of glucose available for use as a fuel source. Insulin helps the released glucose enter the muscle cells, where it can be used for energy production. But insulin levels decline during prolonged exercise, indicating that exercise facilitates the action of insulin so that less of the hormone is required during exercise than at rest. When carbohydrate reserves are low, the body turns more to fat oxidation for energy, and this process is facilitated by cortisol, epinephrine, norepinephrine & growth hormone. Cortisol accelerates lipolysis, releasing free fatty acids (FFA) into the blood so they can be taken up by the cells & used for energy production. But cortisol levels peak & than return to near normal levels during prolonged exercise. When this happens, the catecholamines & growth hormone (GH) taken over cortisol’s role. The two primary hormones involved in the regulation of fluid balance are aldosterone & antidiuretic hormone (ADH). When plasma volume or blood pressure decreases, the kidneys form an enzyme called rennin that converts angiotensinogen into angiotensin I, which later becomes angiotensin II. Angiotensin II increases peripheral arterial resistance, raising the blood pressure. 7. Angiotensin II also triggers the release of aldosterone from the adrenal cortex. Aldosterone promotes sodium reabsorption in the kidneys, which in turn causes water retention, thus increasing the plasma volume.

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ADH is released in response to increased plasma osmolarity (= the ratio of solute to fluid). When osmoreceptors in the hypothalamus sense this increase, the hypothalamus triggers ADH release from the posterior pituitary. ADH acts on the kidneys promoting water conservation. Through this mechanism, the plasma volume is increased, which results in dilution of the plasma solutes. Blood osmolarity decreases.

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