Hormonal Responses to Exercise PDF

HORMONAL RESPONSES TO EXERCISE Chapter 5 Lecture Outline Neuroendocrinology. Hormones: Regulation and Action. Hormonal Control of Substrate Mobilization during Exercise.  Neuroendocrinology Branch of physiology focused on control systems Nervous system releases neurotransmitters to rel...

HORMONAL RESPONSES TO EXERCISE Chapter 5 Lecture Outline Neuroendocrinology. Hormones: Regulation and Action. Hormonal Control of Substrate Mobilization during Exercise.  Neuroendocrinology Branch of physiology focused on control systems Nervous system releases neurotransmitters to relay messages from nerve to nerve or from nerve to tissues Endocrine system releases hormones from endocrine glands in the blood to reach target tissues Hormones (ligands) bind to specific proteins (receptors) on target tissues and alter the activity of those tissues Ligand-receptor interaction causes a response in the target cell called signal transduction Classes of Hormones Hormones can be divided based on chemical make up into amino acid derivatives peptides proteins steroids Classes of Hormones The structure of a hormone determines its mechanisms of transport signal transduction (how it exerts it effects) The most important chemical characteristic is whether the hormone can dissolve in water or cross the plasma membrane (lipid bilayer) Lipophilic hormones – lipid-soluble Cross membrane easily, don’t dissolve in water Lipophobic hormones – water-soluble Don’t cross membrane, do dissolve in water  Hormone Effectiveness Hormone effect on a tissue is influenced by: Number of receptors available for binding Plasma concentration of the hormone  Blood hormone concentration Plasma concentration of a hormone determined by: Rate of secretion of hormone from the endocrine gland Magnitude of input Excitatory or inhibitory input Rate of metabolism or excretion of hormone Hormone inactivation at the receptor and/or removal by liver and kidneys Quantity, capacity and affinity of transport proteins Steroids and thyroid hormones are transported bound to a protein but to exert their effects they need to be “free” to interact with the receptor Changes in plasma volume During exercise, plasma volume ↓ which causes a slight ↑ in hormone concentration in plasma Check your understanding __________ release hormones directly into the blood to alter the activity of tissues possessing receptors to which that hormone can bind. The ____________ and ___________ determine the magnitude of the hormone effect at the tissue level. The plasma hormone concentration can be changed by altering the rate of ___________ or ___________ and ___________ of the hormone, the quantity, capacity and affinity of ____________, and the plasma ________. Hormone secretion can be controlled by several factors EXAMPLE: Insulin secretion is determined by sum of inhibitory vs. stimulatory input Metabolism and Excretion of Hormones Many hormones are altered or destroyed upon binding Excess hormones are removed from the blood by: Liver – metabolizes hormones (major site of hormone metabolism) Kidneys – metabolize or excrete excess hormones into the urine During exercise, what happens to blood flow to the liver and kidneys? How might this impact the rate of hormone metabolism and excretion during exercise? How, then, would this impact blood hormone concentration levels during exercise?  Hormone-receptor interactions Hormones are carried to all tissues but only affect those tissues with specific receptors (proteins) capable of binding those hormones Magnitude of effect dependents on: Concentration of the hormone Number of receptors on the cell Affinity of the receptor for the hormone Downregulation:↓ in receptor number in response to chronically high concentration of hormone Upregulation: ↑ in receptor number in response to chronically low concentration of hormone Chemicals with similar “shape” as a hormone will compete for the limited receptor sites. Receptors can be located in various parts of the cell: Membrane Cytoplasm Nucleus Mechanisms of Hormone Action Altering activity of DNA to modify protein synthesis Steroid hormones Activating second messengers via G protein Cyclic AMP Ca++ Inositol triphosphate Diacylglycerol Altering membrane transport Insulin via tyrosine kinase Altering Activity of DNA in Nucleus Lipophilic Hormones Steroids and thyroid hormones Receptor in the cytoplasm (translocation) or in the nucleus Slow-acting, longer lasting effects Mechanism of Steroid Hormone Action  Membrane Transport Lipophobic Hormones Hormones bind receptors located on the outer surface of the cell membrane and activate carrier molecules in or near the membrane to increase movement of some ion or substrate from outside to inside the cell  Second Messengers Some hormones cannot easily cross cell membranes because these hormones are too large or highly charged These hormones exert their effects by binding to a receptor on the membrane surface and activating a G protein located in the membrane. The G protein is the link between the hormone-receptor interaction and the subsequent events inside the cell. The G protein may activate an enzyme in the membrane or open an ion channel to allow Ca++ to enter the cell Second Messengers Glycogen Glucose Caffeine phosphorylase + + hormone sensitive lipase Triglycerides FFAs Second Messengers Ca2+ Channel Activation G-protein can activate Ca2+ ion channels Ca2+ enters the cell and activates calmodulin Activation of membrane- * bound phospholipase C → * Phosphotidylinositol (PIP2) is hydrolyzed to: Inositol triphosphate (IP3) → intracellular Ca2+ release Diacylglycerol → activates * Protein Kinase C These second messengers are not independent because changes in one can affect * Second messengers action of the other. Check your understanding The hormone-_________ interaction triggers events at the cell Changing the ___________ of the hormone, the _______ of receptors on the cell, or the _________ of the receptor for the hormone will all influence the magnitude of the effect. Hormones bring about their effects by activating/suppressing genes to alter _______________ activating ____________ messengers modifying membrane ___________ Hormones: Regulation and Action Hormones are secreted from endocrine glands Major glands include: Hypothalamus and pituitary glands Thyroid and parathyroid glands Adrenal glands Pancreas Testes and ovaries Growth Hormone Secreted by anterior pituitary gland Stimulates release of insulin-like growth factors (IGFs) IGF-1 responsible for muscle hypertrophy Essential for normal growth of all tissues Stimulates amino acid uptake and protein synthesis Long bone growth Growth hormone spares plasma glucose Opposes insulin action, reduces the use of plasma glucose Increases gluconeogenesis in liver Mobilizes fatty acids from adipose tissue Growth hormone and performance A Closer Look 5.1 GH increases protein synthesis in muscle and long bone growth. Used to treat childhood dwarfism. Also used by athletes and elderly. High doses of GH results in more adverse effects than benefits. No evidence that GH promotes strength gains. Minimal strength gains compared to resistance training alone. Questionable benefits as anti-aging therapy.  Antidiuretic hormone (ADH) or vasopressin Secreted by hypothalamus and stored/released by posterior pituitary gland Reduces water loss from the body to maintain plasma volume Favors reabsorption of water from kidney tubules to capillaries. Release stimulated by high plasma osmolality (low water concentration) and low plasma volume due to sweat loss without water replacement Increases during exercise >60% VO2 max to maintain plasma volume Thyroid gland Stimulated by TSH. Triiodothyronine (T3) and thyroxine (T4). Influences resting metabolic rate. Permissive hormones. Permit full effect of other hormones. Calcitonin. Involved in the regulation of plasma Ca++. Blocks Ca++ release from bone, stimulates excretion by kidneys.  The Adrenal Gland Adrenal gland = two glands Adrenal medulla secretes catecholamines: epinephrine and norepinephrine fast acting hormones part of “fight or flight” response Adrenal cortex secretes steroid hormones derived from cholesterol: Mineralocorticoids (aldosterone) Glucocorticoids (cortisol) Sex steroids (androgens & estrogens)  Adrenal Medulla Catecholamines: Epinephrine (adrenaline) – 80% and norepinephrine – 20% bind adrenergic receptors and change cellular activity via second messengers: Alpha Receptors (α1, α2) Beta Receptors (β1, β2, β3 ) Magnitude and direction (inhibitory vs. excitatory) of the response depends on which ligand binds with which receptor  Aldosterone ▪ Control Na+ and K+ concentration in plasma ▪ Stimulated by: Increased K+ concentration Decreased plasma volume Increased SNS activity to kidney ▪ Regulation of Na+/H2O balance ▪ blood volume and blood pressure Part of renin-angiotensin-aldosterone system All three hormones increase during heavy exercise Cortisol Stimulated by: Exercise Stress Makes amino acids available for tissue repair Maintenance of plasma glucose during long-term fasting and exercise Promotes protein breakdown for gluconeogenesis Stimulates FFA mobilization from adipose tissue Stimulates glucose synthesis Blocks uptake of glucose into cells forcing cells to use more free fatty acids as fuel  Check your understanding ▪ The adrenal cortex secretes ____________ (mineralcorticoid), _________ (glucocorticoid), and ___________ (sex steroids). ▪ Aldosterone regulates __________ balance. Aldosterone secretion _________ with strenuous exercise. ▪ ________ responds to a variety of stressors, including exercise, to ensure that fuel (glucose and free fatty acids) is available, and to make amino acids available for tissue repair.  Adipose Tissue Is an Endocrine Organ In addition to storing triglycerides, adipose tissue also secretes hormones Leptin Suppresses appetite through the hypothalamus Enhances insulin sensitivity and fatty acid oxidation Adiponectin Increases insulin sensitivity and fatty acid oxidation With increased fat mass (obesity) Higher leptin levels and lower adiponectin Leads to type 2 diabetes and low-grade inflammation Exercise does not affect adiponectin or leptin concentration These hormones are more responsive to changes in body weight  The Pancreas – Insulin and Glucagon Insulin ( cells) Promotes the storage of glucose, amino acids, and fats Glucagon ( cells) Promotes the mobilization of FFAs and glucose Somatostatin (from  cells) Controls rate of entry of nutrients into the circulation Digestive enzymes and bicarbonate Into the small intestine The Gonads – Sex Hormones Testosterone – anabolic, androgenic steroid hormone secreted by the testes Promotes tissue (muscle) building Anabolic steroids Originally developed for medical uses Chronic endurance exercise has been shown to decrease plasma [testosterone] Estrogen – steroid hormone secreted by the ovaries Plays a significant role in bone health Chronic endurance training can lead to decreased plasma [estrogen], which can lead to osteoporosis Anabolic Steroids and Performance Initial studies showed no benefit for developing muscle mass In contrast to real-world reports “Subjects” used 10 to 100 times the recommended dosage Also associated with negative side effects Widespread use has led to testing of competitive athletes Most users are not competitive athletes Take more than one steroid in megadoses  Check your understanding Insulin is secreted by the ________ cells of the pancreas and promotes the ________ of glucose, amino acids, and fats. Glucagon is secreted by the ______ cells of the pancreas and promotes the _______ of glucose and fats. Chronic endurance exercise (training) can __________ testosterone levels in males and estrogen levels in females. Muscle as an Endocrine Gland ▪ Skeletal muscle produces myokines when it contracts Stimulate glucose uptake and fatty acid oxidation Promote blood vessel growth in muscle Promote liver glucose production and triglyceride breakdown ▪ Interleukin 6 (IL-6) Both proinflammatory and anti-inflammatory effects ▪ IL-6 produced during exercise promotes anti-inflammatory effect ▪ Regular exercise promotes anti-inflammatory environment Reduction in chronic inflammation and reduced risk of heart disease, type 2 diabetes, and certain cancers Hormonal Control of Substrate Utilization Carbohydrate control is extremely important in the body, especially during exercise During prolonged exercise: carbohydrates are necessary for fat oxidation Greater reliance on blood-born substrates (glucose and FFA) During intense exercise: carbohydrates are the preferred substrate Greater reliance on stored substrate (muscle glycogen) Muscle glycogen breakdown under dual control Plasma epinephrine is a powerful stimulator of glycogenolysis Muscle contraction High-intensity exercise results in greater increases in plasma epinephrine  Muscle Glycogen Utilization Glycogenolysis is related to exercise intensity High-intensity exercise results in greater and more rapid glycogen depletion Check your understanding Glycogen breakdown to _______ in muscle is under the dual control of epinephrine-cyclic AMP and Ca++-calmodulin. The latter’s role is enhanced during exercise due to the increase in ________ from the sarcoplasmic reticulum. In this way, the delivery of fuel (glucose) parallels the activation of contraction. Blood Glucose Control During Exercise The goal of hormones during exercise is to maintain plasma [glucose] during times of increased rate of glucose removal from the circulation Why is it necessary to make sure glucose is in the blood?…Don’t we want it in the cells during exercise?! BRAIN uses glucose! Processes used to maintain plasma [glucose] during exercise: Liver glycogenolysis Liver gluconeogenesis from lactic acid, amino acids, glycerol Mobilization of FFAs from adipose tissue Spares glucose Block glucose entry into cells Forces FFA usage Blood glucose homeostasis during exercise Controlled by hormones. Permissive or slow-acting. Thyroxine, cortisol, and growth hormone. Fast-acting. Epinephrine, norepinephrine, insulin, and glucagon. Thyroid Hormones ▪ Act in a permissive manner to allow other hormones to exert their full effect T3 enhances effect of epinephrine to mobilize free fatty acids from adipose tissue ▪ No real change in T3 and T4 during exercise  Cortisol ▪ Slow-acting hormone ▪ Effects: Stimulates FFA mobilization from adipose tissue Enhances gluconeogenesis in the liver Decreases the rate of glucose utilization by cells ▪ Effect of exercise Increases with exercise intensity ▪ Changes in cortisol may be related to repair of exercise-induced tissue damage  Growth Hormone ▪ Slow-acting hormone ▪ Effects: Supports the action of cortisol ▪ Decreases glucose uptake by tissues ▪ Increases free fatty acid mobilization ▪ Enhances gluconeogenesis in the liver ▪ Exercise effect Increase in plasma growth hormone with increased intensity Greater response in trained runners Check your understanding The hormones _________, __________ and __________ act in a permissive manner to support the actions of other hormones during exercise. ____________ and ____________ also provide a “slow acting” effect on carbohydrate and fat metabolism during exercise. Epinephrine and Norepinephrine ▪ Fast-acting hormones ▪ Maintain blood glucose during exercise by increasing muscle and liver glycogen breakdown increasing FFA mobilization and oxidation blocking glucose uptake by the tissues ▪ Plasma Epinephrine and Norepinephrine increase during exercise Also related to increased heart rate and blood pressure during exercise Epinephrine and Norepinephrine Submaximal intensity exercise ▪ Decreased plasma Epinephrine and Norepinephrine responses to a fixed submaximal workload following endurance training Epinephrine and Norepinephrine Supramaximal intensity exercise ▪ Increased plasma Epinephrine and Norepinephrine in trained individuals  Fast-Acting Hormones Controlling Blood Glucose Insulin vs. Glucagon Insulin Glucagon Uptake and storage of glucose and FFA Mobilization of glucose and FFA fuels ↓ during exercise ↑ during exercise Effects of insulin and glucagon Figure 5.26  Effect On Blood Hormone [Glucose] Epinephrine  Norepinephrine  Growth Hormone  Cortisol  Glucagon  Insulin  Check your understanding Plasma glucose is maintained during exercise by ________ liver glycogen mobilization, using ________ plasma FFA, __________ gluconeogenesis, and ____________ glucose uptake by tissues. The _________ in plasma insulin and the __________ in plasma E, NE, GH, glucagon, and cortisol during exercise control the above mechanisms to maintain glucose concentration. Glucose is taken up by muscle 7-20 times faster during exercise than at rest even though plasma insulin ________. This is due to increases in the number of glucose transporters due to high intracellular ________ and _______ insulin sensitivity. Increased blood ______ also increases the delivery of __________ and __________ which facilitates glucose uptake. An ________ glucose uptake also increases facilitated diffusion of glucose. Training causes ___________ circulating levels of E and NE responses to fixed submaximal exercise and ___________ circulating levels of E and NE responses to supramaximal exercise. Table 5.2: Summary of Hormonal Responses That Serve to Mobilize Fuels and Preserve Blood Glucose During Exercise Hormone Gland Exercise Action Effect on Fuel Response Utilization Glucagon Pancreas ↑ ↑ FFA mobilization Mobilizes fat fuels (alpha-cells) ↑ Glycogenolysis Preserves blood ↓ Glucose uptake glucose Insulin Pancreas ↓ ↑ Glucose, amino Stores fuels (beta-cells) acid, and FFA Lowers blood uptake into tissues glucose  Table 5.2: Summary of Hormonal Responses That Serve to Mobilize Fuels and Preserve Blood Glucose During Exercise Hormone Gland Exercise Action Effect on Fuel Response Utilization Epinephrine Adrenal ↑ ↑ Muscle and liver Mobilizes both fat and Norepinephrine medulla glycogenolysis carbohydrate fuels Cortisol Adrenal ↑ ↑ FFA mobilization Mobilizes fat fuels cortex ↑ Gluconeogenesis Preserves blood ↓ Glucose uptake glucose Growth hormone Anterior ↑ ↑ FFA mobilization Mobilizes fat fuels pituitary ↑ Gluconeogenesis Preserves blood ↓ Glucose uptake glucose FFA mobilization decreases during heavy exercise This occurs in spite of persisting hormonal stimulation for FFA mobilization Possible Reasons Why: 1. High levels of lactic acid promotes re-synthesis of 2 triglycerides 2. Elevated [H+] due to increased lactate inhibits hormone sensitive lipase 3. Inadequate blood flow to adipose 4. Insufficient albumin to 1 transport FFA in plasma Check your understanding The plasma FFA concentration ___________ during heavy exercise even though the adipose cell is stimulated by a variety of hormones to increase triglyceride breakdown to _____________ and _______. This may be due to: (1) the higher H+ concentration, which may inhibit _________ (2) the high levels of lactate during heavy exercise promoting the resynthesis of _______________ (3) an inadequate ___________ to adipose tissue, or (4) insufficient ________ needed to transport the FFA in the plasma.