Endocrine System PDF

Endocrine System Endocrine System – Introduction to Hormones & Hormone Signaling – Endocrine Glands Hypothalamus Anterior & Posterior Pituitary – HPA-Axis (hypothalamic-pituitary-adrenal axis) – Growth Thyroid Gland...

Endocrine System Endocrine System – Introduction to Hormones & Hormone Signaling – Endocrine Glands Hypothalamus Anterior & Posterior Pituitary – HPA-Axis (hypothalamic-pituitary-adrenal axis) – Growth Thyroid Gland – Metabolism Parathyroid Glands Adrenal Glands – Stress Pineal Gland Pancreas – Blood Sugar Regulation Gonads (Ch. 27)  The Endocrine System The Endocrine System regulates homeostasis on a long time scale by releasing and controlling hormones over hours, days, weeks Hormone: chemical released into the blood to regulate distant target cells Endocrinology: the study of hormones and endocrine organs  Endocrine Processes Overall, the major processes that the Endocrine System can regulate: – Reproduction – Growth and Development – Electrolyte, water, nutrient balance of blood – Cellular metabolism and energy balance – Immune defenses  Endocrine Glands Pineal gland Hypothalamus Major Endocrine Glands Pituitary gland – Hypothalamus Thyroid gland – Pituitary Gland Parathyroid glands Anterior Pituitary Posterior Pituitary Thymus – Thyroid Gland – Parathyroid Glands Adrenal glands – Adrenal Glands Pancreas – Pineal Gland Others with partial endocrine Gonads function: Ovary (female) – Pancreas (endocrine portion) Testis (male) – Thymus – Gonads (ovaries and testes) © 2016 Pearson Education, Inc.  Pineal gland Figure 16.1 Location of Hypothalamus selected endocrine Pituitary gland organs of the body. Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads Ovary (female) Testis (male) © 2016 Pearson Education, Inc.  Neural Hormonal input input The Hypothalamus- Hypothalamus Pituitary Axis of Control (secretes) Hormone 1 Endocrine “chain of command” Hypophyseal portal system Anterior pituitary – Hypothalamus (secretes) releasing or inhibiting hormones Hormone 2 – Anterior Pituitary tropic hormones Systemic circulation – Peripheral Endocrine Gland Target endocrine gland hormones (secretes) – Target Cells Hormone 3 change in homeostatic factors General circulation Target cells Physiologic effect  Hypothalamus-Anterior Pituitary The Hypothalamus releases 7 hormones that regulate the release of anterior pituitary hormones releasing hormones: increase release of target hormones in the anterior pituitary inhibiting hormones: decrease release of target hormones in the anterior pituitary 1. Thyrotropin- releasing hormone (TRH) 2. Corticotropin-releasing hormone (CRH) 3. Gonadotropin-releasing hormone (GnRH) 4. Prolactin Releasing hormone (PRH) 5. Dopamine/Prolactin Inhibiting Hormone (PIH) 6. Growth Hormone Releasing Hormone (GHRH) 7. Somatostatin/Growth Hormone Inhibiting Hormone (GHIH)  Hormones and Glands: Hypothalamus: – aldosterone (mineralocorticoid) – ADH – cortisol (glucocorticoid) – oxytocin – DHEA (gonadocorticoid) – releasing and inhibiting DHEA: Dehydroepiandrosterone hormones: GHRH, GHIH, TRH, Adrenal Medulla CRH, GnRH, PIH – Epinephrine, Norepinephrine Anterior Pituitary: Pineal Gland – growth hormone – melatonin – tropic hormones: TSH, ACTH, Pancreas: FSH, LH, PRL – insulin Thyroid Gland – glucagon – thyroid hormone Gonads (see reproductive) – calcitonin – estrogen Parathyroid Gland – progesterone – parathyroid hormone – testosterone Adrenal Cortex  Hormones & Major Processes Growth Hormone & Growth Regulation Thyroid & Metabolism Regulation Parathyroid & Calcium Regulation Cortisol & Stress Regulation Aldosterone à Urinary system Melatonin & Sleep/Wake Cycle Regulation Insulin & Blood Glucose Regulation Estrogen à Female Reproductive Testosterone à Male Reproductive  Regulation of Growth Growth of the whole body requires the synthesis of proteins, lengthening of bones, and increasing size and number of cells In children and adolescents, growth is regulated by growth hormone Other hormones can influence growth: – thyroid hormone – insulin – sex hormones (androgens, estrogens) Also influenced by: – genetics – diet – level of stress/chronic disease Fig. 18-8, p. 672  Growth Hormone Growth hormone (somatotropin) is a hormone that increases growth and metabolism – amino-acid based produced and released: anterior pituitary Functions: – metabolic functions (throughout life): fat breakdown increased blood glucose – growth functions protein synthesis (muscle mass, cellular growth) bone growth increased cell division Regulation: – hormonal: GHRH, GHIH from hypothalamus, negative feedback of IGF-I (insulin-like growth factors) and GH – neural: diurnal rhythms (increase with sleep)  Growth Hormone & IGF’s Growth hormones actions to promote growth are mediated by IGF’s (insulin-like growth factors), also called somatomedins IGF’s: peptide hormones – IGF-I: mainly released into blood by liver, local production by individual tissues stimulates soft tissue cell number and cell size stimulates long bone growth negative feedback to anterior pituitary to decrease GH – IGF-II: fetal development, adult role unknown  Growth Hormone Pathway Stimulus: GHRH (hypothalamus) Production & Release: Growth Hormone made and released by anterior pituitary Targets: – liver: produce IGF’s, breakdown glycogen à glucose stimulates soft tissue cell number and cell size stimulates long bone growth – adipose tissue: breakdown fats à fatty acids – all body cells: growth and metabolism, increase amino acid uptake & protein synthesis, reduce glucose uptake (more glucose in blood), increase fatty acid uptake Regulation: – IGF’s à negative feedback on anterior pituitary – GH à negative feedback on anterior pituitary – GHIH (hypothalamus)  Hypothalamus Figure 16.5 secretes growth Growth- Feedback Inhibits GHRH release hormone–releasing promoting Stimulates GHIH release hormone (GHRH), and Anterior GHIH (somatostatin) and metabolic pituitary actions of Inhibits GH synthesis growth and release hormone (GH). Growth hormone (GH) Indirect actions Direct actions (growth- (metabolic, promoting) anti-insulin) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Fat Carbohydrate Skeletal Extraskeletal metabolism metabolism Increases, stimulates Reduces, inhibits Increased protein Initial stimulus Increased cartilage Increased Increased blood synthesis, and formation and fat breakdown glucose and other Physiological response cell growth and skeletal growth and release anti-insulin effects proliferation Result © 2016 Pearson Education, Inc.  Growth Hormone Syndromes hypersecretion of growth hormone: gigantism (whole body enlarged) or acromegaly (enlarged extremities) hyposecretion of growth hormone: dwarfism growth hormone replacement therapy is effective if diagnosed before epiphyseal plate closure GH abuse: bodybuilders, athletes, elderly – minimal evidence for muscle strength or stature ‫زﯾﺎدة اﻟﻘﺎﻣﺔ‬ increase in adults, can cause fluid retention, joint and muscle pain, diabetes, cancer  Thyroid Hormone Thyroid Hormones: T3 and T4 are the major metabolic hormones of the body – lipid-soluble, plasma protein bound – T4: tetra-iodothyronine; stored and secreted form – T3: tri-iodothyronine; more potent, ‫اﻟﺣﻧﺟرة‬ biologically active form Produced and released: Thyroid Gland: bow- tie shaped organ located below the larynx ( Function: increased metabolic rate, increased heat production, increased growth and CNS development, increased SNS activity (stress) Regulation: – hormonal: TRH (Hypothalamus), TSH (Anterior Pituitary), negative feedback – neural: body temperature, stress  Thyroid Hormone Pathway Stimulus: TRH (hypothalamus), TSH (anterior pituitary) Production & Release: made and released by the thyroid gland Targets: – all body cells: – increased metabolism & heat production – increased tissue growth and development – blood vessels: increased SNS receptors to maintain blood pressure Regulation: – ** see also synthesis & transport – T3 and T4 negative feedback to hypothalamus and anterior pituitary – hormonal inhibition: GHIH, dopamine, glucocorticoids – neural: cold (in infants), stress  Hypothalamus Figure 16.7 Regulation of thyroid hormone secretion. TRH TSH inhibits the release of TRH Short loop negative feedback Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits © 2016 Pearson Education, Inc.  Figure 16.8 The thyroid gland. Hyoid bone Thyroid Epiglottis cartilage Common Superior carotid thyroid artery artery Parafollicular cells (secrete calcitonin) Inferior Isthmus of thyroid thyroid gland artery Follicular cells (secrete thyroid hormone) Trachea Left subclavian artery Colloid-filled Left lateral follicles lobe of Aorta thyroid gland Gross anatomy of the thyroid gland, Photomicrograph of thyroid gland anterior view follicles (315×) © 2016 Pearson Education, Inc. Thyroid Hormone Synthesis Thyroid Hormone is made from the amino acid tyrosine and iodide (I-) Synthesis STEPS: 1) Thyroglobulin with tyrosines synthesized in follicular cells 2) iodide actively transported into follicular colloid cells 3) iodide converted to iodine 4) iodine attached to tyrosine in colloid 5) T3 and T4 made in colloid by attaching to thyroglobulins 6) T3-thyroglobulins and T4 – thyroglobulins back into follicular cells 7) T3 and T4 cleaved from thyroglobulins diffuse into blood follicular cells  Figure 16.9 Synthesis of thyroid Thyroid follicular cells hormone. Colloid 1 Thyroglobulin is synthesized and discharged into the follicle lumen. Tyrosines (part of thyroglobulin molecule) Capillary 4 Iodine is attached to tyrosine in colloid, forming DIT and MIT. Golgi apparatus Rough Thyro- ER Iodine globulin 3 Iodide DIT MIT colloid is oxidized to iodine. Iodide (I−) 2 lodide (I−) is trapped (actively transported in). T4 5 Iodinated tyrosines are T3 linked together to form T3 Lysosome and T4. T4 6 Thyroglobulin colloid is endocytosed and combined T3 with a lysosome. 7 Lysosomal enzymes T4 Colloid in cleave T4 and T3 from lumen of T3 thyroglobulin and hormones follicle diffuse into bloodstream. To peripheral tissues monoiodotyrosine (MIT) and diiodotyrosine (DIT)  T4 to T3 conversion T4 – tetra-iodothyronine: – T4 is the major form of thyroid hormone that is stored and secreted by the thyroid T3 – tri-iodothyronine: – 80% of T3 is made from T4 by removing and iodide in the liver or kidneys, 20% is secreted as T3 by the thyroid gland – T3 is 10 times more potent and the more biologically active form  Thyroid Hormone Syndromes Hyperthyroidism: excess T3 and T4 due to autoimmune disease, tumors. In adults causes high metabolism, sweating, tachycardia, irregular heartbeat, anxiety, protruding eyeballs – Grave’s disease (autoimmune) bulging eyes Hypothyroidism: low T3 and T4 due to lack of iodine in diet, TRH/TSH deficiency, thyroid gland disease in adults causes low metabolism, cold, ‫ ﺑطﯾﺋﺎ‬sluggish, dry skin, puffy eyes, edema – myxedema, cretinism (mental disability) – goiter: enlarged thyroid gland due to iodine deficiency goiter: enlarged thyroid  Myxedema severely advanced hypothyroidism  Calcitonin Calcitonin: reduces blood calcium levels Produced and released: by thyroid gland parafollicular cells Function: inhibits bone breakdown, stimulates calcium storage in bones, reduces blood calcium Regulation: – blood (humoral): increased blood calcium NOTE: not required in humans, if thyroid is removed, little to no effect on patient calcium homestasis  Parathyroid Hormone Parathyroid Hormone: increases calcium in the blood – amino-acid based Produced and released: by Parathyroid Glands, 3-4 tiny glands on the posterior side of thyroid Function: increase plasma Ca2+, decreased plasma PO43-, stimulates Vitamin D Regulation: Thyroid gland – blood (humoral): Ca2+ levels in blood, thyroid gland (calcitonin) Parathyroid NOTE: required for calcium glands homeostasis, removal can be fatal  Figure 16.11 The parathyroid glands. Pharynx (posterior aspect) Capillary Thyroid Parathyroid gland cells Parathyroid (secrete glands parathyroid Esophagus hormone) Trachea Oxyphil cells © 2016 Pearson Education, Inc.  Parathyroid Hormone Pathway Stimulus: low blood calcium Target: – Bone: increase in Ca2+ release from bone fluid to ECF via calcium pumps in osteocytes and osteoblasts increase in bone breakdown, Ca2+ and PO4 release via stimulation of osteoclasts – Kidneys: increase in blood calcium retention via kidneys decrease in blood phosphate via kidney elimination increase in Vitamin D activation by kidneys – Small intestine (Vitamin D needed for calcium absorption in diet) Regulation: – blood (humoral): high Ca2+ in blood directly inhibits parathyroid hormone production and release  Hypocalcemia (low blood Ca2+) Figure 16.12 Effects of parathyroid hormone on bone, the kidneys, and the intestine. PTH release from parathyroid gland Osteoclast activity Ca2+ reabsorption Activation of in bone causes Ca2+ in kidney tubule vitamin D by kidney – and PO43 release into blood Ca2+ absorption from food in small intestine Initial stimulus Physiological response Ca2+ in blood Result © 2016 Pearson Education, Inc.  Parathyroid Hormone Syndromes hyperparathyroidism: usually by tumors -can cause bone loss, nervous system depression, muscle weakness, weak reflexes, kidney stones – can be secondary response to low blood calcium due to kidney failure Hypoparathyroidism: following gland removal (thyroid surgery), or magnesium deficiency – can cause muscle spasm, nervous system excitability, convulsions, paralysis, DEATH  Adrenal Glands Adrenal Glands: small, capped glands above the kidneys Adrenal Adrenal medulla cortex 1. Adrenal Cortex: outer region 2. Adrenal Medulla: middle region Adrenal Medulla: Catecholamines Adrenal Medulla: middle region of the adrenal glands Hormones: epinephrine, norepinephrine Target: SNS organ targets Functions: enhance sympathetic effects, Adrenal medulla stress regulation, blood pressure Regulation: sympathetic nervous system Catecholamines (epinephrine and norepinephrine) Adrenal Cortex: Steroids Adrenal Cortex: outer region of the adrenal glands Steroid Hormones: Adrenal 1) mineralocorticoids (aldosterone) cortex 2) glucocorticoids (cortisol) Mineralocorticoids 3) sex hormones (androgens) (aldosterone) Glucocorticoids (cortisol) and sex hormones DHEA (dehydro- epiandrosterone)  Figure 16.13 Microscopic structure of the adrenal gland. Hormones Capsule secreted Zona Aldosterone glomerulosa Zona Adrenal gland fasciculata Cortex Medulla Cortex Cortisol and Kidney androgens Zona reticularis Medulla Adrenal medulla Epinephrine and norepinephrine Drawing of the Photomicrograph histology of the (115×) adrenal cortex and a portion of the adrenal medulla © 2016 Pearson Education, Inc.  Mineralocorticoids (Aldosterone) Mineralocorticoids- primarily aldosterone Fluid Balance: – increases Na+ in the blood, retained from urine – decreases K+ in the blood, eliminated in urine – Water balance follows Na+ increase, blood volume increases, blood pressure increases Aldosterone deficiency is FATAL, due to loss of blood volume. More in Ch. (Renin-Angiontensin System, kidneys) Aldosterone Mineralocorticoid (adrenal cortex hormone)  Gonadocorticoids (Sex Hormones) Sex Hormones: are androgens adrenal cortex is a secondary site of Dehydroepiandrosterone production, gonads are primarily (adrenal cortex hormone) responsible for sex hormones, other tissues can also produce androgens Androstenedione Estrone (adipose tissue) – DHEA – mainly from adrenal cortex - weak Testosterone Estradiol precursor to testosterone, mainly involved Androgens in secondary sex characteristics in females (male sex hormones) during puberty (growth spurt, hair Estriol patterns, sex drive) masculinizing effect in excess – estrogen – mainly from ovaries – testosterone – mainly from testes More in Ch. Reproductive  Glucocorticoids (Cortisol) Glucocorticoids: primarily Cortisol Metabolism: – increase blood glucose Cortisol – sequester blood glucose for the brain Glucocorticoid – increase protein breakdown (adrenal cortex hormone) – increase fat breakdown Related to Stress Response/SNS/Epin/nor Immune Suppression: – blocks inflammation pathways – blocks antibody production  Cortisol Cortisol: maintains blood glucose during fasting, enhances the stress response during trauma and inhibits the immune system Adrenal gland Cortex – steroid-based hormone Medulla Cortex Produced and released: by Adrenal Cortex Kidney Function: increases gluconeogenesis, breakdown of fats to increase fatty Medulla acids, breakdown of protein to increase amino acids, anti-inflammatory and anti-immune effects Regulation: – hormonal: CRH by hypothalamus and ACTH by anterior pituitary – neural: stress  Cortisol Pathway Stimulus: CRH (Hypothalamus) and ACTH (anterior pituitary) Targets: all body cells – gluconeogenesis: make glucose from fatty acids and amino acids, breakdown fat, breakdown protein – immune system: inhibition Production and Release: Adrenal Cortex Regulation: – neural: stress, diurnal Rhythms- highest cortisol in morning, lowest at night – hormonal: Negative Feedback: high cortisol levels inhibit CRH and ACTH  Stress Diurnal rhythm Hypothalamus Cortisol Pathway Corticotropin-releasing hormone (CRH) Glucocorticoids inhibit the release of CRH Anterior pituitary Long loop negative feedback Adrenocorticotropic hormone (ACTH) Adrenal cortex Cortisol Blood glucose (by stimulating gluconeogenesis Metabolic fuels and inhibiting glucose uptake) and building blocks Blood amino acids available to help (by stimulating protein resist stress degradation) Blood fatty acids (by stimulating lipolysis) Fig. 19-9, p. 696  Cortisol Syndromes hyposecretion: usually both mineral and glucocorticoids involved (a) Young boy – Addison’s disease: weight loss, low prior to onset blood glucose, low blood ions, of the condition dehydration, hypotension excess glucocorticoids: anterior pituitary tumors, other tumors, glucocorticoid treatment for immune diseases – can mimic diabetes with persistent elevation in blood glucose, muscle and bone loss, water and salt retention, edema, high blood pressure – Cushing’s syndrome: “moon face”, increased abdominal and back of the neck fat, chronic infections, muscle and bone weakening (b) Only four months later, the same boy displaying a “moon face” characteristic of Cushing’s syndrome (hypersecretion of Cortisol)  Insulin insulin: lowers blood glucose by allowing cells to transport glucose in – amino-acid based Produced and released by: pancreas Functions: glucose uptake in muscle and fat cells, glycogen storage, inhibit glucose Pancreas production Regulation: – blood (humoral): levels of nutrients in blood – neural: PSNS post-eating (inhibited by SNS) – hormonal: increased by glucagon, epinephrine, thyroxine, glucocorticoids, decreased by somatostatin Fig. 19-15, p. 709  Pancreatic Cells Endocrine portion: Islets of Langerhans are 1% of the pancreas – alpha (α) cells - glucagon – Beta cells (β) - insulin – delta cells (D) - somatostatin – F cells – pancreatic polypeptide Exocrine portion: 99% – acinar cells - digestive enzymes – duct cells – NaHCO3 solution  Insulin Effects Insulin increases during absorptive, post- digestive state of high nutrient intake and facilitates nutrient use and storage – lowers blood glucose production and storage of glycogen in liver and muscle increase glucose transport into cells inhibit glycogen breakdown and gluconeogenesis in liver – lowers fatty acids à storage of fat production and storage of triglycerides increase transport fatty acids into adipose tissue inhibit triglyceride breakdown – lowers amino acids à storage of protein production and storage of protein increase transport of amino acids into cells inhibit protein breakdown  Type I and Type II Diabetes Mellitus Type I Diabetes: lack of insulin secretion from pancreas – can be treated with injected insulin Type II Diabetes: normal insulin secretion, lack of target cell response to insulin, high blood glucose – insulin treatment does not help – diet, exercise high blood glucose due to lack of storage and use of glucose in body cells high glucose elimination in urine, polyuria, dehydration, reduced blood volume, reduced blood flow to brain, other tissues polyphagia – excessive hunger, food intake due to lack of nutrients IN body cells  Glucagon glucagon: increased blood glucose – amino-acid based Produced and released by: pancreas Functions: glucose synthesis, glucose release, glycogen breakdown Pancreas Regulation: – blood (humoral): low levels of blood glucose – neural: stimulated by SNS – hormonal: inhibited by insulin and somatostatin  Glucagon opposes Insulin Glucagon Effects Oppose Insulin: glucagon is increased between meals, during “fasting” states, ensuring brain receives enough glucose – increased blood glucose decreased glycogen production and storage increase gluconeogenesis and glycogenolysis in liver – increased fatty acids and ketones increased lipolysis in adipose tissue increased ketogenesis – decreased protein synthesis inhibit liver protein synthesis increased protein degradation in liver NO effect on muscle protein, NO increase in blood amino acids  Control of Blood Glucose Insulin and glucagon act as antagonistic hormones to control blood glucose levels Most of the time both of these hormones are found in the blood, it is the ratio of the two that determines which is dominant Figure 16.18 Insulin and Stimulates glucose uptake by cells glucagon from the pancreas regulate Insulin Tissue cells blood glucose Stimulates levels. glycogen formation Pancreas Glucose Glycogen Blood Liver glucose falls to normal range. IM BA LA NC Stimulus E Blood glucose level BALANCE: Normal blood glucose level (about 90 mg/100 ml) Stimulus Blood IM BA glucose level LA NC Blood E glucose rises to normal range. Pancreas Glucose Glycogen Liver Stimulates glycogen Glucagon breakdown © 2016 Pearson Education, Inc.