Exercise Physiology: Theory and Application to Fitness and Performance By Scott Powers & Edward Howley Ch 5 Cell Signaling and the Hormonal Responses to Exercise Summary Created by Dan Hechler Class Lecture Exercise Physiology I Dr. Laurie Milliken, UMass Boston, Fall 2015 Neuroendocrinology 1. Neuroendocrine -Endocrine System releases hormones (chemical messengers) -Nervous System uses neurotransmitters 2. Endocrine Glands -Ductless glands that release hormones directly into the blood 3. Exocrine glands -Release products into ducts (sweat glands, digestive glands) 4. Pancreas -Both Exocrine (digestive enzymes) and Endocrine (insulin and glucagon) Hormones 1. -Travel in blood to their specific target organs -Receptors are specific to hormones such that only the correct hormone will fit. -Each cell has 2,000 to 10,000 specific receptors 2. Several classes based on chemical makeup -Amino acid derivatives -Peptides/Protein -Steroids Blood Hormone Concentration The effect a hormone has on a tissue is determined by plasma concentration Determine by: 1. Rate of secretion of hormone from endocrine gland -Magnitude of input -Stimulatory versus inhibitory input 2. Rate of metabolism or excretion of hormone -At receptor and by the liver and kidneys 3. Quantity of transport protein -Ex. Steroid hormones 4. Changes in plasma volume
Example of Factors That Influence Secretion of Hormones Hormone Receptor Interactions 1. Hormones only affect tissue with specific receptors 2. Magnitude of effect dependent on: -Concentration of hormone -Number of receptors on cell -Affinity of receptor for hormone 3. Down regulation -Decrease in receptor number in response to high concentration of hormone 4. Up regulation -Increase in receptor number in response to low concentration of hormone Mechanisms of Hormone Action 1. Altering membrane transport -Ex. Insulin 2. Altering activity of DNA to modify protein synthesis -Steroid Hormones (Only Hormone to DIRECTLY modify DNA) 3. Activating second messengers via G protein -Cyclic AMP -Ca +2 -Inositol Triphosphate -Diacylglycerol 4. Tyrosine Kinase -Insulin and Growth Hormone
Mechanism of Steroid Hormone Action 1. Must be carried through carrier protein (due to being fat and not soluble in blood) but can diffuse across lipid bilayer (both fat) and then attaches to receptor protein to be carried into the nucleus to interact with DNA Cyclic AMP Second Messenger Mechanism 1. Hormone attaches to receptor which goes through cell membrane and activates G protein which activates Adenlylate Cyclase which produces ATP resulting in Cyclic AMP which will activate a protein kinase which can activate specific cellular responses. The Phosphodiesterase breaks down the Cyclic AMP to inhibit this process.
Calcium and Phospholipase C Second Messenger Mechanisms Insulin Receptor Hormones: Regulation and Action 1. Hormones are secreted from endocrine glands -Hypothalamus and pituitary glands -Thyroid and parathyroid -Adrenal Glands -Pancreas -Testes and ovaries
Hypothalamus and Pituitary Gland 1. Hypothalamus -Controls secretions from pituitary gland -Releases hormones or factors 2. Anterior Pituitary Gland (Endocrine Connection to Hypothalamus) -Adrenocorticotropic hormone (ACTH) -Follicle-stimulating hormone (FSH) -Luteinizing hormone (LH) -Melanocyte-stimulating hormone (MSH) -Thyroid-stimulating hormone (TSH) -Growth Hormone (GH) -Prolactin 3. Posterior Pituitary Gland (Direct Neural Connection to Hypothalamus) -Oxytocin -Antidiuretic Hormone (ADH) Hormones of the Anterior Pituitary Gland
Influences on Growth Hormone Release 1. Stimulates release of insulin-like growth factors (IGFs) -IGF-1 in muscle responsible for muscle growth 2. Essential growth of all tissues -Amino Acid uptake and protein synthesis -Promotes long bone growth (femur) 3. Spares plasma glucose -Reduces use of plasma glucose (opposes action of insulin) -Increases gluconeogenesis (creation of new glucose through non-cho carbon substrates such as pyruvate, lactate, glycerol, and glycogenic amino acids) (increase synthesis of glucose in liver) -Mobilizes fatty acids from adipose tissues 4. Side effects are acromegaly (too much growth hormone) and diabetes 5. Responds via negative feedback loop Growth Hormone and Performance 1. GH increases protein synthesis in muscle and long bone growth -Used to treat childhood dwarfism and used by athletes and elderly 2. More adverse effects than benefits 3. No evidence GH promotes strength gains -Protein synthesis is collagen, not contractile protein 4. Difficult to detect usage by athletes Growth Hormone
Posterior Pituitary Hormones -Posterior Pituitary (Neurohypophysis) stores hormones and releases them as needed via neural stimulation (these hormones are produced in hypothalamus and secreted to the neurohypophysis -Hormones 1. Oxytocin -Stimulator of smooth muscle -Involved with release of breast milk 2. Antidiuretic hormone (ADH) or vasopressin -Stimulated by exercise -Reduces water loss from body to maintain plasma volume via reabsorption of water from kidney tubules to capillaries -Release stimulated by high plasma osmolality and low plasma volume (due to sweat loss without water replacement) -Increases during exercise >60% VO 2 max (to maintain plasma volume) Thyroid Gland 1. Stimulated by Thyroid Stimulating Hormone (TSH) 2. Triiodothyronine (T 3 ) and Thyroxin (T 4 ) -Establishment of metabolic rate -Permissive hormones (Permit full effect of other hormones) 3. Calcitonin -Regulation of plasma Ca +2 (minor role) -High Ca +2 level triggers release -Blocks release from bone, stimulates excretion by kidneys Parathyroid Gland 1. Parathyroid Hormone -Primary hormone in plasma Ca +2 regulation -Stimulates Ca +2 release from bone -Stimulates Ca +2 reabsorption by kidneys -Converts Vitamin D 3 into hormone that increases Ca +2 absorption from GI tract Adrenal Medulla (Located On top of Kidney) 1. Secrets the catecholamine s -Epinephrine (E) and Norepinephrine (NE) -Primary secretion is E (80%) and is part of the fight or flight response 2. Bind to adrenergic receptors -Alpha -Beta -Effects depend on hormone used and receptor type
Adrenal Cortex (Outer Layer) 1. Secretes steroid hormones -Derived from cholesterol 2. Mineralocorticoids -Aldosterone -Maintenance of plasma Na + and K + 3. Glucocorticoids -Cortisol -Regulation of plasma glucose 4. Sex Steroids -Androgens and estrogens -Support prepubescent growth Aldosterone (Adrenal Cortex) 1. Control of Na + reabsorption and K + secretion -Maintain electrolyte (Na + and K + ) balance in extracellular fluids 2. Regulation of blood volume and blood pressure -Part of renin-angiotensin-aldosterone system -Vasoconstrictor (off sets low blood pressure when plasma blood volume decreases and stimulates aldosterone release which increases sodium reabsorption) -All three hormones increase during exercise 3. Stimulated by -Increased K + concentration -Decreased plasma volume
Cortisol (Adrenal Cortex) 1. Maintenance of plasma glucose -Promotes protein breakdown for gluconeogenesis -Stimulates FFA mobilization and increases lipolysis -Stimulates glucose synthesis -Blunts the effects of insulin (decrease glucose use) Blocks uptake of glucose into cells Promotes the use of FFA as fuel -Net effect=mobilization of fuel 2. Stimulated by: -Stress via ACTH Part of General Adaptation Syndrome -Exercise 3. Anti-inflammatory agent -Trained runners are in a hypercortisolism state -Remains elevated post exercise (tissue recovery and repair) Cortisol Adipose Tissue Is an Endocrine Organ 1. Addition to storing triglycerides, adipose tissue also secretes hormones -Leptin Influences appetitive through hypothalamus (decreased leptin increases eating) Enhances insulin sensitivity and fatty acid oxidation -Adiponectin Increases insulin sensitivity and fatty acid oxidation 2. With increased fat mass (obesity) -Higher Leptin levels and lower adiponectin Leptin resistance -Leads to type 2 diabetes (insulin resistance) and low-grade inflammation
Muscle As An Endocrine Gland 1. 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 2. Interleukin 6 (IL-6) Both pro-inflammatory and anti-inflammatory IL-6 produced during exercise promotes anti-inflammatory effect Inhibits production of TNF-alpha 3. Regular exercise promotes anti-inflammatory Reduction in chronic inflammation and reduced risk of heart disease, type 2 diabetes, and certain cancers Pancreas (Both Exocrine and Endocrine Functions) 1. Secretes: -Insulin (Beta Cells) Promotes the storage of glucose, amino acids, and fats (anabolic functions) Lack of insulin is called diabetes mellitus (Type I) -Glucagon (Alpha Cells) Promotes the mobilization of fatty acids and glucose -Somatostatin (Gamma Cells) Controls rate of entry of nutrients into the circulation -Digestive enzymes and bicarbonate Into the small intestine
Kidneys 1. Hormone erythropoietin which regulates red blood cell production EPO important in adapting to training and altitude 2. Kidneys also release renin which is a hormone and enzyme involved in BP control and fluid and electrolyte balance. Testes and Ovaries 1. Testosterone -Released from testes -Anabolic Promotes tissue building Performance enhancement Androgenic steroid Promotes masculine characteristics 2. Estrogen and Progesterone -Released from ovaries -Establish and maintain reproductive function -Levels vary throughout the menstrual cycle Table 5.2 Pg. 107-108 Overall Summary Of Hormones Hormonal Control of Substrate Mobilization During Exercise 1. Systems work to maintain normal blood glucose levels during exercise -Liver has 80 grams of glucose before exercise -Oxidation rates of glucose can reach 1g/min in heavy or prolonged activity Muscle Glycogen Utilization 1. Glycogenolysis (splitting of glycogen into glucose) is related to exercise intensity -High Intensity=greater use of glycogen resulting in depletion 2. Plasma epinephrine powerful stimulator of glycogenolysis -High Intensity=increased plasma epinephrine 3. Even with epinephrine blocked via propranolol muscle glycogen was still mobilized
Control of Muscle Glycogen Utilization 1. Breakdown of muscle glycogen is under Dual control -Epinephrine-cyclic AMP Via beta-adrenergic receptors -Ca +2 -calmodulin Enhanced during exercise due to Ca +2 release from sarcoplasmic reticulum 2. Evidence for role of Ca +2 -calmodulin in glycogenolysis from the propranolol study Blood Glucose Homeostasis During Exercise Plasma glucose maintained through FOUR Processes 1. Mobilization of glucose from liver glycogen stores 2. Mobilization of FFA from adipose tissue Spares blood glucose 3. Gluconeogenesis from amino acids, lactate, and glycerol 4. Blocking the entry of glucose into cells Forces use of FFA as fuel Controlled by TWO Types of Hormones 1. Permissive or slow acting Thyroxin, cortisol, growth hormone 2. Fasting-Acting Epinephrine, norepinephrine, insulin, glucagon
Slow Acting Hormones (Permissive) 1. Thyroid Hormones (Permissive Manner) -T 3 enhances effect of epinephrine to mobilize free fatty acids from adipose tissue -NO REAL CHANGE in T 3 and T 4 during exercise 2. Cortisol (Permissive Manner) -Stimulate FFA mobilization from adipose tissue -Enhance gluconeogenesis in liver -Decrease rate of glucose utilization by cells (forcing more FFA) Effects of Exercise -Decrease during low-intensity exercise -Increase during high intensity exercise Above approx. 60% VO 2 Max Changes in cortisol may be related to repair of exercise-induced tissue damage
Growth Hormone (Permissive Manner) Effects: -Supports the action of cortisol Decreases glucose uptake by tissues Increases FFA mobilization Enhances gluconeogenesis in the liver Exercise Effect -Increase in plasma GH with increased intensity -Greater response in trained runners compared to untrained Fast Acting Hormones Epinephrine and Norepinephrine 1. Fasting acting 2. Maintain blood glucose during exercise Muscle glycogen mobilization Increasing liver glucose mobilization Increasing FFA mobilization Interfere with glucose uptake for cells 3. Plasma E and NE INCREASE during exercise -Related to increased heart rate and blood pressure during exercise (NE bigger role) 4. Decreased plasma E and NE following training Decreased plasma E and NE following training; Graph below shows submaximal training and adaptations to E and NE release following weeks of training at that level.
Insulin and Glucagon (Fast Acting Hormones) 1. Insulin -Uptake and storage of glucose and FFA -Plasma concentration DECREASES during exercise -Decreased insulin response following training 2. Glucagon -Mobilization of glucose and FFA fuels -Plasma concentration increases -Decreased response following training Insulin and Glucagon secretion influenced by catecholamine s (E and NE)
Changes in Plasma Insulin DURING EXERCISE -Decrease during exercise (due to it being anabolic hormone) Changes in Plasma Glucagon DURING EXERCISE -Increases during exercise and more in trained individuals Blood glucose levels DO NOT change during exercise so level of blood glucose CANNOT be the stimulus of change of Insulin and Glucagon SO Epinephrine and Norepinephrine control the release of Glucagon and Insulin.
Summary of Hormonal Response During Exercise Hormones Increasing Glucose Metabolism 1. Glucagon (increases glycogenolysis and gluconeogenesis) 2. Epinephrine (increases glycogenolysis) 3. Norepinephrine (increase glycogenolysis) 4. Cortisol (increases gluconeogenesis) Hormones Increasing Fat Metabolism 1. Cortisol 2. Glucagon 3. Epinephrine 4. Growth Hormone Summary of Plasma Glucose During Exercise 1. Plasma glucose is maintained during exercise by increasing liver glycogen mobilization, using more plasma FFA, increasing gluconeogenesis, decreasing glucose uptake by tissues. 2. Decrease in plasma insulin and increase in plasma E, NE, GH, glucagon, and cortisol during exercise control these mechanisms to maintain glucose concentration. 3. Glucose is taken up seven to twenty times faster during exercise than at rest EVEN with a decrease in plasma insulin. 4. Training causes a reduction in E, NE, Glucagon, and insulin responses to exercise. Free Fatty Acid & Exercise 1. FFA mobilization dependent on hormone sensitive lipase (HSL) 2. FFA mobilization DECREASES during heavy exercise -Occurs in spite of persisting hormonal stimulation for FFA mobilization 3. May be due to: -High levels of lactate Promotes resynthesis of triglycerides -Elevated H + inhibits HSL (hormone sensitive lipase) -Inadequate blood flow to adipose tissue -Insufficient albumin to transport FFA in plasma
Effect of Lactate on FFA Mobilization