Stress: Living and Performance, an Endocrine story

1. Stress:Living and Performance, an Endocrine story Drew Deppen BSc

2. Are you stressed yet?

3. “If you only follow guru’s, you’ll be nothing but average.”Stu McGill • Stress Guru’s • Walter Cannon • Hans Seyle • Bruce McEwen • Robert Sapolsky – Why Zebra’s don’t get Ulcers • Peter Sterling • Katrina Borer – Exercise Endocrinology

4. Stress • 11 different definitions • “Stress is a specific response by the body to a stimulus that disturbs or interferes with the ‘normal’ physiological equilibrium of an organism.” • Stressor is anything that causes an organism to experience stress.

5. The Stress Response • Walter Cannon • Homeostasis • Constancy in an open system requires mechanisms that act to maintain this constancy. • Steady-state conditions require that any tendency toward change automatically meets with factors that resist change. • The regulating system that determines the homeostatic state consists of a number of cooperating mechanisms acting simultaneously or successively. • Homeostasis does not occur by chance, but is the result of organized self-government

6. The Stress Response • Hans Selye • General Adaptation Syndrome • Now called the Stress Response • Injected Rats with ovary extract • Peptic ulcers • Enlarged adrenals • Shrunken immune tissue • Body has a similar set of responses to a broad array of stressors • Sounds counterintuitive to have same physiology when too hot, and too cold • Built around the fact that muscles need energy when stressed • Chances of you running for food, or from being food are high • If stressors go on for too long, they can make you sick

7. Types of Stressors • Acute Physical Stress • Fight of Flight response • Highly adapted to handle this type • Chronic Physical Stress • Drought, famine, parasites, infections • Fairly adapted to handle these things • Psychological and Social Stress • Western society, traffic jams, depression, anxiety • Fairly recent in evolutionary timeframe • Chess players can place metabolic demands on their bodies equal to high class athletes at peak events

8. SNS and PSNS • Sympathetic Nervous System • 4F’s • Fighting, Flighting, Frighting, and Sexing • Adrenals are connected to SNS via a preganglionic synapse! • Stress Response increases SNS tone • Parasympathetic Nervous System • Rest and Digest • Inhibited with Stress response

9. Endocrine Review • Hypothalamus • Brain control center secreting releasing and inhibitory hormones, Oxytocin, ADH, Dopamine • Pituitary • Releasing ‘trophic’ hormones • Adrenals • Glucocorticoids, Mineralcorticoids, Androgens, Estrogens, and Catecholamines • Other endocrine glands as well • HPA axis - this is the main ‘axis’

10. 1- Pineal gland 1b - Hypothalamus 2- Pituitary gland 3- Thyroid gland 4- Thymus 5- Adrenal gland 6- Pancreas 7- Ovary 8- Testis 1b Endocrine Anatomy

11. Metabolism ↑ Protein Degradation ↓ Protein Synthesis ↑ Amino Acids to liver ↓ Amino Acids to muscle ↑ Gluconeogenesis ↑ Glycogen liver synthesis ↑ Lipolysis ↑ Truncal and Facial lipogenesis and fat deposition Immune ↓ Inflammatory cytokines ↓ Capillary permeability ↓ Phagocytosis ↓ T-lymphocytes Blood ↑ Vasoconstriction ↑ blood volume ↑ RBC and Leukocyte synthesis Kidney ↑ GFR ↑ Na retention – blood volume Brain ↑ ↓ Mood ↑ Senses ↑ Appetite Glucorticoid functions

12. General Stress Response • You get ‘Stressed’ • Muscles need energy NOW • Glucose, Protein, Fatty Acids mobilized • HR, BP, Respiration increases • Vasodilatation in skeletal muscle and skin • Vasoconstriction in kidneys and GI tract • Decrease reproductive stuff (during physical stress) • Sorry boys and girls - ↓ erections and ovulations • Decrease Immunity • Secrete Endorphins – POMC cells • Senses Sharpen • Cognition actually improves • How did I get out of this one last time?

13. Acute Physical Stress (Phase 1) • Stressor introduced • SNS system activated • Anticipation • Even thinking about certain scenarios • Cyclical SNS activity • Catecholamines • Positive feedback causing ↑ NE, Epi • Glucagon secreted (insulin inhibited)

14. Acute Physical Stress (Phase 2) • Hypothalamus activated in minutes • CRH, TRH, ADH • Causes the secretion of trophic hormones • HPA axis fast to react • CRH, and ADH releases ACTH which releases glucocorticoids • Intra/Intercellular cytokines released • TNF – a, IL-1, IL-4 • ADH, PRL, Endorphins, Enkephalins also secreted • Insulin, Estrogen, Testosterone, and GH inhibited during stress • After stress GH may increase

15. Acute Physical Stress (Phase 3) • Nutrient Partitioning • Different depending on type of exercise • Mobilize Energy • ↑ hepatic glucose production • Lipolysis • Proteolysis • Gluconeogenesis • Glycogenolysis

16. Energy Mobilisation • Non stressful situations • Body will store energy for later times • Stress! • ↑ SNS ↓ PSNS (stops energy storage) • Release glucocorticoids, glucagon, NE/E • FFA’s, glycerol released, glycogen oxidized, GNG • Glucocorticoids actually block energy uptake in muscles and adipocytes • Exercising muscle overcomes this mechisms --? Crazy • Energy is shunted from non-exercising muscle to exercising muscle

17. Acute Physical Stress (Phase 4) • Recovery • PS tone increases and SNS decreases • Restores homeostasis, fuel storage, structural repair • Insulin rebound after high intensity followed by a rapid decrease in NE • GH increases along with IGF’s • Early and Late Phase recovery may be different • Cellular glucose uptake • Adaptation Occurs • Basal Hormonal Conc. changes • PS and SNS changes • Smaller NE response to same exercise bouts

18. Hormones Secreted CRH ACTH Glucocorticoids Glucagon ADH Prolactin Catecholamines Endorphins IL-1, IL-6, TNF – a Hormones Inhibited Insulin Testosterone Estrogen GH IGF’s Acute Physical Stress

19. Immune Response • Common misconception that stress ↓ IR • Initially it enhances immunity – esp innate • More inflammatory cells mobilized, antibodies released in saliva • May need to fight infection from a tiger bite • Prolonged stress ↓ IR • Glucocorticoid, NE/E levels start destroying lymphocytes • Can be good to get rid of old cells • Chronic stress response can lead to autoimmunity • Constantly ramping up IR may lead you toward ‘friendly fire’

20. Psychological Stress • Same stress response • Body gears up to utilize a huge amount of energy • Never gets to use it • Metabolically costly • No tiger to run from when road-raging • Bad deal • Metabolic Syndrome • Cardiovascular Disease • Ulcers • Autoimmune Disease • Depression • Cancer risk not associated! • May be associated with outcomes

21. Building Blocks for psychological stress • Outlets for frustration • Rats shocked with and without block to gnaw on • Humans can imagine outlets • Great way to relieve stress is to stress someone else • Social Support • Primates may have a decreased response when surrounded by other primates • If others are strangers it doesn’t help • Crying on someone’s shoulder physiologically helps! • People with spouses live longer • Predictability • Rats shocked after a warning have ↓ response • Blitzkrieg bombings • London hit every night, suburbs sporadically – who developed greater responses? • Control • Rats that can press lever to inhibit a shock then remove level – huge response • People afraid of flying but driving is more dangerous – I can control my driving. • Perception of things worsening • 2 rats – 1 gets 10 shocks/hour, other 50 • Next day both get 25 shocks per hour – stress response is different

22. Food Consumption • How many people eat more when stressed? • CRH ↓ appetitebut Glucocoricoids ↑ appetite • Uses leptin secreted from adipocytes to blunt ‘fullness’ • Glucocorticoids help mobilize energy, inhibit storage • What’s going on? Released at different times • CRH released immediately, glucocorticoids released slowly • Also the clearance is similar – CRH fast, Cortisol slow • Prolonged stressor will cause appetite to ↑ • Appetite for calorie dense food is preferentially simulated – ice cream!

23. Apples and Pears Vs. • Apple shaped people prefer to store fat in abdominal area • Pear shaped people prefer to store fat in gluts • Abdominal adipocytes are more sensitive to cortisol in presence of insulin to store fat • Waist-hip ration is a more accurate predictor for CVD and metabolic syndrome than obesity alone • FFA’s more easily transported to liver

25. Coping Strategies • Exercise • Gets rid of the energy, must be voluntary and regular, aerobic is better for stress reduction • Meditation • Any kind of parasympathetic activation activity done regularly • Gain control/predictability • Can be a double edge sword • Social support • Both utilizing others when needed and feeling need for others • Religion/spirituality • Allows for social support in fairly healthy decision group • Cognitive flexibility • Chose the right coping strategies • Study for the test before hand, and talk about how it doesn’t matter afterwards • Conditioning • Sharpen the on and off times • Stress yourself and learn to deal with it – make it a choice • 80/20 Rule • 80% of stress reduction occurs within first 20% effort • You have to decide to make a change

26. Exercise effects • Cardiovascular and Respiratory • Redistribute blood flow, regular BP • Blood clotting in anticipation of injury • Modulate Pain • Mediate tissue repair post-event • Engage Immune defenses post-event • Not a ‘true’ homeostatic mechanism • Spontaneous activity in positive energy balance?

27. Endocrine support • Sympathoadrenal Catecholamines • NE, Epi • Hypothalamo-pituitary-adrenal axis (HPA) • CRH, ACTH, Glucocorticoids • Endogenous Opiates • Endorphins (POMC cells) • Hydromineral hormones • ADH, Aldosterone, Ang II

29. Acute Physical Stress

30. Low intensity Exercise (under 50% VO2) • Below 50% VO2 max • Oxidative metabolism • Type 1 fibers – red (mitochondria) • 40 - 85% energy from FFA’s • Carb sparing mechanism • 100mg/dl glucose in plasma + 100g liver glycogen • 85% utilized during normal daily activity • 50% used during overnight fast • 10 – 20kg of TG’s storage • ↓ Insulin slightly • Hexokinase has a high affinity for Glucose even in absence of Insulin • Glut -4 transporter tranlocates to membrane with muscle contraction • ↑ NE slightly • ↓ Glucose

31. Moderate Intensity Exercise • 50-75% VO2 max • Mixed metabolic demands • Endogenous and peripheral storage • Mixed fiber types IC- IIA • Endogenous lipids and glycogen primarily used (80%) • FFA’s used are from abdominal area/upper body • ↓ Insulin with a spike after activity • ↑ GH after mild duration of activity • ↑ Glucocorticoid during and after activity • ↑ Lactate • ↑ Glucose with a drop after duration • ↑ NE during and after activity

32. High Intensity Exercise • >80% VO2 max • 25% lipids and 75% Glucose energy • Mostly intracellular glycogen • Stimulate PFK and PDH • Increases lactate – inhibits lipolysis • Excess acetyl Co-A produces acetyl-Carnitine, Coenzyme A • Activates Malonyl Co-A – inhibits fat oxidation • ALL are non-insulin mechanisms to utilize carb catabolism • Equal amts TG and peripheral adipose tissue • FFA blocked from entering circulation by NE/E • White type IIX fibers • Creatine phosphate systems – early fatigue • ↑ NE/E • ↑ GH • ↑ Glucagon • ↓ Insulin with rebound spike after activity • ↑ IL-6 • Stim GH, PRL, CRH, and ADH secretion

34. Physical Stress

37. Carb supplementation ↑ Carb metabolism, ↓ lipolysis Insulin mediated Stimulates PDH and ACC (makes malonyl CoA) Inhibits Carnitine Glucose will cause a mild hypoglycemia for 20mins Fructose will not - ↓ insulin response ↓ Fatigue when eaten after 2 hours moderate intensity Lipid Suppementation ↑ Lipid Oxidation After several days of adaptation to high fat diet ↑ FFA uptake in muscle ↑ Lipoprotein Lipase Improves endurance in low and moderate intensity exercise Spares muscle gylcogen and PCr systems Creatine Good stuff for power movements Nutrition during exercise

39. Big Picture • Is stress bad? • Yes • And no • Stress can do our physiology very well when applied under ‘normal’ circumstances • When we get endocrine adaptation things can go well and we can make gains • Stress can also be bad in excess and when we don’t have any way to channel it • Like anything else in life

40. Coping Strategies • Exercise • Gets rid of the energy, must be voluntary and regular, aerobic is better for stress reduction • Meditation • Any kind of parasympathetic activation activity done regularly • Gain control/predictability • Can be a douple edge sword • Social support • Both utilizing others when needed and feeling need for others • Religion/spirituality • Allows for social support in fairly healthy decision group • Cognitive flexibility • Chose the right coping stradegie • Study for the test before hand, and talk about how it doesn’t matter afterwards • Conditioning • Sharpen the on and off times • Stress yourself and learn to deal with it – make it a choice • 80/20 Rule • 80% of stress reduction occurs within first 20% effort • You have to decide to make a change