THE ENDOCRINE SYSTEM D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM COMPARISON OF ENDOCRINE AND NERVOUS SYSTEMS • NERVOUS SYSTEM • “WIRED” • CHEMICAL SIGNAL AT TARGET CELL • RAPID • BRIEF DURATION • CLOSE ANATOMICAL PROXIMITY • ENDOCRINE SYSTEM • “WIRELESS” • CHEMICAL SIGNAL AT TARGET CELL • SLOW • LONG DURATION • SPECIFIC RECEPTORS CATEGORIES OF HORMONES • PEPTIDES • AMINES • STEROIDS PEPTIDES • • • • HYDROPHILIC DISSOLVED IN PLASMA RECEPTOR ON CELL SURFACE cAMP OR CALCIUM AS SECOND MESSENGERS • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS PEPTIDE HORMONES • • • • • • • • HYPOTHALAMIC PITUITARY PANREATIC PARATHYROID GI KIDNEY LIVER HEART AMINES • THYROID HORMONE • CATECHOLAMINES • ALL DERIVED FROM AMINO ACID TYROSINE • UNIQUE SYNTHETIC AND SECRETORY PATHWAYS STEROIDS • LIPOPHILIC • RECEPTOR IN CYTOPLASM • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS • ADRENAL CORTICAL • GONADAL • PLACENTAL PLASMA CONCENTRATION OF HORMONES • • • • DEPENDS ON RATE OF SECRETION NEGATIVE FEEDBACK NEUROENDOCRINE REFLEXES DIURNAL RHYTHMS TYPES OF ENDOCRINE DISORDERS • HORMONE EXCESS • HORMONE DEFICIENCY • DECREASED RESPOSIVENESS OF RECEPTORS HYPOTHALAMUS AND POSTERIOR PITUITARY NEUROSECRETORY NEURONS VASOPRESSIN OXYTOCIN ANTERIOR PITUITARY HYPOTHALAMUS POSTERIOR PITUITARY SYSTEMIC ARTERY SYSTEMIC VEIN HYPOTHALAMUS AND ANTERIOR PITUITARY NEUROSECRETORY NEURONS ANTERIOR PITUITARY: •TSH •ACTH •PROLACTIN •GROWTH HORMONE •LH •FSH HYPOTHALAMUS POSTERIOR PITUITARY HYPOTHALAMIC-HYPOPHYSEAL PORTAL SYSTEM • VESSELS PASS THROUGH STALK OF PITUITARY FROM HYPOTHALAMUS TO ANTERIOR PITUITARY • CARRY HYPOTHALAMIC REGULATORY HORMONES HYPOTHALAMIC REGULATORY HORMONES • TROPIC HORMONES • CONTROL THE SECRETION OF OTHER HORMONES BY ACTING ON ENDOCRINE TISSUE HYPOTHALAMIC RELEASING AND INHIBITING HORMONES • CONTROL THE SECRETION OF ANTERIOR PITUITARY TROPIC HORMONES • TRH:THYROTROPIN-RELEASING HORMONE • PRH:PROLACTIN RELEASING HORMONE • PIH:PROLACTIN INHIBITING HORMONE • GHRH:GROWTH HORMONE RELEASING HORMONE • GHIH: GROWTH HORMONE INHIBITING HORMONE • CRH:CORTICOTROPHIN RELEASING HORMONE HIERARCHICAL CONTROL INPUT HYPOTHALAMUS HORMONE 1 (RELEASING/INHIBITING) H/H PORTAL SYSTEM ANTERIOR PITUITARY ENDOCRINE GLAND HORMONE 2 (TROPIC) SYSTEMIC CIRCULATION HORMONE 3 SYSTEMIC CIRCULATION TARGET CELLS NEGATIVE FEEDBACK INPUT HYPOTHALAMUS HORMONE 1 (RELEASING/INHIBITING) H/H PORTAL SYSTEM ANTERIOR PITUITARY ENDOCRINE GLAND HORMONE 2 (TROPIC) SYSTEMIC CIRCULATION HORMONE 3 SYSTEMIC CIRCULATION TARGET CELLS ANTERIOR PITUITARY HORMONES:TSH • THYROID GLAND • THYROID HORMONES (T3 & T4 ) ANTERIOR PITUITARY HORMONES:ACTH • ADRENAL CORTEX • CORTISOL ANTERIOR PITUITARY HORMONES:PROLACTIN • MAMMARY GLANDS • BREAST GROWTH AND MILK SECRETION ANTERIOR PITUITARY HORMONES: GROWTH HORMONE • • • • • LIVER SOMATOMEDINS BONE SOFT TISSUE GROWTH • MANY TISSUES • INTERMEDIARY METABOLISM • INCREASE OR DECREASE ANTERIOR PITUITARY HORMONES: LH & FSH: ACT ON GONADS • LH:LETEINIZING HORMONE • SEX HORMONE SECRETION • F: ESTROGEN AND PROGESTERONE • M: TESTOSTERONE • FSH:FOLLICLE STIMULATING HORMONE • GAMETE PRODUCTION • OVA • SPERM CONTROL OF GROWTH • • • • GENETIC DIET DISEASE HORMONES ANTERIOR PITUITARY HORMONES: GROWTH HORMONE • • • • • LIVER SOMATOMEDINS BONE SOFT TISSUE GROWTH • MANY TISSUES • INTERMEDIARY METABOLISM • INCREASE OR DECREASE METABOLIC ACTIONS OF GROWTH HORMONE • MOBILIZES TRIGLYCERIDE FAT STORED IN ADIPOSE TISSUE • CONSERVES GLUCOSE FOR BRAIN GROWTH PROMOTING ACTIONS OF GROWTH HORMONE • SOFT TISSUES: STIMULATES CELL DIVISION, INCREASES SIZE OF CELLS • STIMULATES ALMOST ALL ASPECTS OF PROTEIN SYNTHESIS • INHIBITS PROTEIN DEGRADATION • PROMOTES UPTAKE OF AMINO ACIDS GROWTH PROMOTING ACTIONS OF GROWTH HORMONE • BONE: PROMOTES GROWTH OF LONG BONES • THICKNESS • LENGTH • AT END OF ADOLESCENCE, SEX HORMONES STOP THIS ACTION GROWTH HORMONE ACTS THROUGH SOMATOMEDINS • PEPTIDE MEDIATORS • PRODUCED IN LIVER AND OTHER TISSUES • ALSO PARACRINE EFFECTS GHRH AND GHIH • ANTAGONIST IN CONTROL OF GROWTH HORMONE SECRETION • NEGATIVE FEEDBACK • DIURNAL RHYTHM: GH SECRETED AT NIGHT • EXERCISE, STRESS, HYPOGLYCEMIA ABNORMAL GH SECRETION • DEFICIENCY: DWARFISM, REDUCED MUSCLE STRENGTH, DECREASED BONE DENSITY • EXCESS:GIGANTISM, ACROMEGLY THE THYROID GLAND • • • • • OVER TRACHEA THYROGLOBULIN TETRAIODOTHYRONINE TRIIODOTHYRONINE IODINE REQUIRED FROM DIETARY INTAKE THYROID HORMONE’S EFFECTS • • • • METABOLIC RATE: INCREASED BMR CALOROGENIC: INCREASED HEAT PRODUCTION SYMPATHOMIMETIC: FLIGHT OR FIGHT CARDIOVASCULAR:INCREASES RESPONSIVENESS OF HEART • GROWTH: ESSENTIAL FOR NORMAL GROWTH • NERVOUS SYSTEM:DEVELOPMENT AND ADULT ACTIVITY REGULATION OF THYROID SECRETION STRESS HYPOTHALAMUS - + COLD IN CHILDREN TRH ANTERIOR PITUITARY TSH THYROID GLAND THYROID HORMONE TARGET ORGANS ABNORMALITIES OF THYROID FUNCTION • HYPO • REDUCED BMR • POOR TOLERANCE OF COLD • GAIN OF WEIGHT • FATIGUE • SLOW, WEAK PULSE • SLOW REFLEXES AND MENTATION • MYXEDEMA • GOITER • CRETINISM • HYPER • GRAVE’S DISEASE:TSI • EXOPHTALMOS • GOITER THE ADRENAL GLANDS • CORTEX: STEROID HORMONES SECRETED • MEDULLA: CATECHOLAMINES CORTEX: STEROID HORMONES SECRETED • MINERALOCORTICOIDS • GLUCOCORTICOIDS • SEX HOMONES MINERALOCORTICOIDS • • • • ALDOSTERONE ELECTROLYTE BALANCE BLOOD PRESSURE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM GLUCOCORTICOIDS • • • • • CORTISOL GLOCONEOGENESIS PERMISSIVE ACTIONS STRESS ADAPTATION ANTI-INFLAMITORY AND IMMUNOSUPPRESSANT REGULATION OF CORTISOL SECRETION HYPOTHALAMUS STRESS + CRH + - DIURNAL RHYTHM ANTERIOR PITUITARY INCREASED BLOOD GLUCOSE BLOOD AA BLOOD FATTY ACIDS ACTH - ADRENAL CORTEX CORTISOL TARGET ORGANS SEX HOMONES • ANDROGENS (TESTOSTERONE) • ESTROGENS • LESS THAN GONADS ADRENAL OVERSECRETION • MINERALCORTICOIDS: SODIUM RETENTION, POTASSIUM DEPLETION • CORTISOL:EXCESS GLUCONEOGENESISEXCESS GLUCOSE DEPOSITED AS FAT • ANDROGEN:MASCULINIZATION, PSEUDOHERMAPHODITISM, PRECOCIOUS PSEUDOPUBERTY, NO EFFECT IN ADULT MALES ADRENAL INSUFFICIENY • • • • • CORTEX: ADDISON’S DISEASE POOR RESPONSE TO STRESS LACK OF PERMISSIVE ACTION POTASSIUM RETENTION HYPOTENSION MEDULLA: CATECHOLAMINES • A MODIFIED SYMPATHETIC POST GANGLIONIC NEURON • EPINEPHRINE ACTIONS OF EPINEPHRINE • MIMICS SYMPATHETIC NS • MOBILIZES STORED FAT AND CARBOHYDRATE • HEART AND BLOOD VESSELS GENERAL ADAPTATION SYNDROME • • • • • • • FLIGHT OR FIGHT EPINEPHRINE CRH-ACTH-CORTISOL RENIN-ANGIOTENSIN-ALDOSTERONE VASOPRESSIN COORDINATED BY HYPOTHALAMUS CAN BE INDUCED PSYCHOSOCIALLY CONTROL OF FUEL METABOLISM • • • • • • • GLYCOGENESIS GLYCOGENOLYSIS GLUCONEOGENESIS PROTEIN SYNTHESIS PROTEIN DEGRADATION FAT SYNTHESIS FAT BREAKDOWN ANABOLISM VS CATABOLISM • BUILD UP VS BREAKDOWN OF LARGE MOLECULES • ANABOLISM REQUIRES ENERGY (ATP) • CATABOLISM:ENERGY PRODUCTION PANCREATIC HORMONES • INSULIN • GLUCAGON INSULIN: ACTION ON BLOOD SUGAR • BETA CELLS IN ISLETS OF LANGERHANS: INSULIN • FACILITIES GLUCOSE ENTRY INTO CELLS • STIMULATES GLYCOGENESIS • INHIBITS GLYCOGENOLYSIS • INHIBITS GLUCONEOGENESIS INSULIN: ACTION ON FAT • INCREASES TRANSPORT INTO ADIPOSE CELLS • PROMTES TRIGLYCERIDE SYNTHESIS • INHIBITS LIPOLYSIS INSULIN: ACTION ON PROTEIN • PROMOTES UPTAKE OF AA BY MUSCLE AND OTHER TISSUE • PROMOTES PROTEIN SYNTHESIS • INHIBITS PROTEIN DEGRADATION CONTROL OF INSULIN SECRETION • NEGATIVE FEEDBACK: BLOOD SUGAR • BLOOD AA • GI HORMONES • PARASYMPATHETIC ACTIVITY TWO TYPES OF DIABETES MELLITUS • TYPE I: AUTOIMMUNE DESTRUCTION OF BETA CELLS, LACK OF INSULIN SECRETION • TYPE II: REDUCED SENSITIVITY OF INSULIN RECEPTORS ACUTE EFFECTS OF DIABETES MELLITUS • • • • • • • • • • • • EXTRACELLULAR GLUCOSE EXCESS GLUCOSE IN URINE EXCESS FLUID LOSS CIRCULATORY FAILURE RENAL FAILURE NERVOUS SYSTEM MALFUNCTION DUE TO DEHYDRATION EXCESSIVE FOOD INTAKE PROGRESSIVE WEIGHT LOSS MOBILIZTION OF FAT KETOSIS ACIDOSIS COMA AND DEATH GLUCAGON • PANCREATIC ALPHA CELLS • GENERALLY OPPOSES ACTIONS OF INSULIN • DECREASE GLYCOGEN SYNTHESIS • PROMOTE GLYCOGENOLYSIS • STIMULATE GLUCONEOGENESIS • PROMOTES FAT BREAKDOWN • ONLY IN LIVER: PROTEIN CATABOLISM EPINEPHRINE, CORTISOL, AND GROWTH HORMONE • ALL INCREASE BLOOD GLUCOSE AND FATTY ACIDS • CORTISOL INCREASES BLOOD AA AND DECREASES MUSCLE PROTEIN • GH DECREASES BLOOD AA AND INCREASES MUSCLE PROTEIN CONTROL OF CALCIUM METABOLISM • PARATHYROID HORMONE • CALCITONIN • VITAMIN D PARATHYROID HORMONE • • • • RAISES FREE PLASMA CALCIUM FROM BONE CONSERVATION IN KIDNEYS INCREASES INTESTINAL ABSORPTION (VIA VITAMIN D ACTIVATION) • REGULATED BY FREE CALCIUM IN PLASMA (NEGATIVE FEEDBACK) CALCITONIN • C CELLS OF THYROID GLAND • DECREASE IN CA MOBILIZATION FROM BONE • NOT AS IMPORTANT AS PTH AND VITAMIN D VITAMIN D • ACTUALLY A HORMONE • RELEASED FROM SKIN BY SUNLIGHT • TWO STEP ACTIVATION: LIVER AND KIDNEYS • INCREASES CALCIUM ABSORPTION IN INTESTINE PTH HYPOSECRETION • LOW CALCIUM AND HIGH PHOSPHATE • MUSCLE SPASMS • MENTAL CHANGES VITAMIN D DEFICIENCY • IMPARED ABSORPTION OF CALCIUM • PTH MAINTAINS PLASMA LEVEL AT EXPENSE OF BONES • RICKETS IN CHILDREN • OSTEOMALACIA IN ADULTS
