4/23/2018. Endocrine System: Overview. Endocrine System: Overview

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1 Endocrine System: Overview With nervous system, coordinates and integrates activity of body cells Influences metabolic activities via hormones transported in blood Response slower but longer lasting than nervous system Examples of control and integration Reproduction Growth and development Maintenance of electrolyte, water, and nutrient balance of blood Regulation of cellular metabolism and energy balance Mobilization of body defenses Endocrine System: Overview Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands Hypothalamus is neuroendocrine organ Mixed glands: Pancreas, gonads, placenta Other tissues and organs that produce hormones Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart Figure 16.1 Location of selected endocrine organs of the body. Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads Ovary (female) Testis (male) 1

2 Chemistry of Hormones Two main classes Amino acid-based hormones Amino acid derivatives, peptides, and proteins Many are at least partially water soluble and travel through blood without need of stabilizing binding protein Often short-lived, existing for seconds or minutes Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones Most are lipophilic and poorly water soluble; need binding during blood transport Often long-lived, existing for minutes to hours Mechanisms of Hormone Action Though hormones circulate systemically only cells with receptors for that hormone affected Target cells - must have specific receptors to which hormone binds Hormones alter target cell activity Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels Stimulate synthesis of enzymes or other proteins Activate or deactivate enzymes Induce secretory activity Stimulate mitosis Mechanisms of Hormone Action Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location 1. Plasma membrane receptors respond to water-soluble hormones (all amino acid based hormones except thyroid hormone) 2. Intracellular/nuclear receptors respond to lipid-soluble hormones (steroid and thyroid hormones) 2

3 Plasma Membrane Receptors and Secondmessenger Systems camp signaling mechanism: 1. Hormone (first messenger) binds to receptor 2. Receptor activates G protein 3. G protein activates adenylate cyclase 4. Adenylate cyclase converts ATP to camp (second messenger) 5. camp activates protein kinases that phosphorylate proteins 6. Activated kinases phosphorylate various proteins, activating some and inactivating others 7. camp is rapidly degraded by enzyme phosphodiesterase 8. Intracellular enzymatic cascades have huge amplification effect Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Slide 6 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd 1 Hormone (1st messenger) (1st messenger) messenger binds receptor. Adenylate cyclase Extracellular fluid G protein (G s) Receptor GTP GTP camp ATP 5 camp activates protein kinases. GDP GTP Inactive protein kinase Active protein kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor 3 G protein 4 Adenylate activates G activates cyclase converts protein (G s). adenylate ATP to camp (2nd cyclase. messenger). Intracellular Receptors and Direct Gene Activation Steroid hormones and thyroid hormone 1. Diffuse into target cells and bind with intracellular receptors 2. Receptor-hormone complex enters nucleus; binds to specific region of DNA 3. Prompts DNA transcription to produce mrna 4. mrna directs protein synthesis 5. Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell 3

4 Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Slide 6 Extracellular fluid Cytoplasm Nucleus Steroid hormone Receptor protein mrna Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Receptorhormone complex 2 The receptorhormone complex enters the nucleus. Receptor Binding region DNA 3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mrna. New protein 5 The mrna directs protein synthesis. Target Cell Specificity Target cells must have specific receptors to which hormone binds, for example ACTH receptors found only on certain cells of adrenal cortex Thyroxin receptors are found on nearly all cells of body Target Cell Activation Target cell activation depends on three factors Blood levels of hormone Relative number of receptors on or in target cell Up-regulation Down-regulation Affinity of binding between receptor and hormone 4

5 Control of Hormone Release Blood levels of hormones Controlled by negative feedback systems Vary only within narrow, desirable range Endocrine gland stimulated to synthesize and release hormones in response to Humoral stimuli Neural stimuli Hormonal stimuli Figure 16.4a Three types of endocrine gland stimuli. Slide 1 Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca 2+ in blood) Parathyroid glands Thyroid gland (posterior view) PTH Parathyroid glands Stimulus: Low concentration of Ca 2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca 2+. Figure 16.4b Three types of endocrine gland stimuli. Slide 3 Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine. 5

6 Figure 16.4c Three types of endocrine gland stimuli. Slide 1 Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Adrenal cortex Gonad (Testis) Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones. Hormones in the Blood Hormones circulate in blood either free or bound Steroids and thyroid hormone are attached to plasma proteins All others circulate without carriers Concentration of circulating hormone reflects Rate of release Speed of inactivation and removal from body Hormones in the Blood Hormones removed from blood by Degrading enzymes Kidneys Excretion based on water solubility, size Liver Half-life time required for hormone's blood level to decrease by half Varies from fraction of minute to a week 6

7 Onset of Hormone Activity Some responses ~ immediate Some, especially steroid, hours to days Some must be activated in target cells Duration of Hormone Activity Limited Ranges from 10 seconds to several hours Effects may disappear as blood levels drop Some persist at low blood levels The Pituitary Gland and Hypothalamus Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe) Neural tissue Anterior pituitary (lobe) (adenohypophysis) Glandular tissue 7

8 Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Slide 1 Paraventricular nucleus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Axon terminals Hypothalamichypophyseal tract Posterior lobe of pituitary Hypothalamus Supraoptic nucleus Inferior hypophyseal artery Oxytocin ADH 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). 2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary. 3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Slide 1 Anterior lobe of pituitary Superior hypophyseal artery 2 Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary. 3 In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary Hypothalamus 1 When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. Hypophyseal portal system Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. A portal system is two capillary plexuses (beds) connected by veins. Posterior Pituitary and Hypothalamic Hormones Oxytocin and ADH Each composed of nine amino acids Almost identical differ in two amino acids Oxytocin Strong stimulant of uterine contraction Released during childbirth Hormonal trigger for milk ejection Acts as neurotransmitter in brain 8

9 ADH (Vasopressin) Inhibits or prevents urine formation Regulates water balance Targets kidney tubules reabsorb more water Release also triggered by pain, low blood pressure, and drugs Inhibited by alcohol, diuretics High concentrations vasoconstriction Anterior Pituitary Hormones Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL) Anterior Pituitary Hormones All are proteins All except GH activate cyclic AMP secondmessenger systems at their targets TSH, ACTH, FSH, and LH are all tropic hormones (regulate secretory action of other endocrine glands) 9

10 Growth Hormone (GH) GH release chiefly regulated by hypothalamic hormones Growth hormone releasing hormone (GHRH) Stimulates release Growth hormone inhibiting hormone (GHIH) (somatostatin) Inhibits release Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Feedback Inhibits GHRH release Stimulates GHIH release Inhibits GH synthesis and release Anterior pituitary Hypothalamus secretes growth hormone releasing hormone (GHRH), and GHIH (somatostatin) Growth hormone (GH) Indirect actions (growthpromoting) Direct actions (metabolic, anti-insulin) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Skeletal Extraskeletal Fat metabolism Carbohydrate metabolism Increases, stimulates Reduces, inhibits Increased cartilage formation and skeletal growth Increased protein synthesis, and cell growth and proliferation Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Initial stimulus Physiological response Result Growth Hormone (GH, or Somatotropin) Produced by somatotropic cells Direct actions on metabolism Increases blood levels of fatty acids; encourages use of fatty acids for fuel; protein synthesis Decreases rate of glucose uptake and metabolism conserving glucose Glycogen breakdown and glucose release to blood (anti-insulin effect) 10

11 Growth Hormone (GH, or Somatotropin) Indirect actions on growth Mediates growth via growth-promoting proteins insulin-like growth factors (IGFs) IGFs stimulate Uptake of nutrients DNA and proteins Formation of collagen and deposition of bone matrix Major targets bone and skeletal muscle Thyroid-stimulating Hormone (Thyrotropin) Produced by thyrotropic cells of anterior pituitary Stimulates normal development and secretory activity of thyroid Release triggered by thyrotropin-releasing hormone from hypothalamus Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus Figure 16.8 Regulation of thyroid hormone secretion. Hypothalamus TRH Anterior pituitary TSH Thyroid gland Target cells Thyroid hormones Stimulates Inhibits 11

12 Gonadotropins Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Secreted by gonadotropic cells of anterior pituitary FSH stimulates gamete (egg or sperm) production LH promotes production of gonadal hormones Absent from the blood in prepubertal boys and girls Gonadotropins Regulation of gonadotropin release Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty Suppressed by gonadal hormones (feedback) Adrenocorticotropic Hormone (Corticotropin) Secreted by corticotropic cells of anterior pituitary Stimulates adrenal cortex to release corticosteroids 12

13 Adrenocorticotropic Hormone (Corticotropin) Regulation of ACTH release Triggered by hypothalamic corticotropinreleasing hormone (CRH) in daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can alter release of CRH Glucocorticoids Keep blood glucose levels relatively constant Maintain blood pressure by increasing action of vasoconstrictors Cortisol (hydrocortisone) Only one in significant amounts in humans Cortisone Corticosterone Glucocorticoids: Cortisol Released in response to ACTH, patterns of eating and activity, and stress Prime metabolic effect is gluconeogenesis formation of glucose from fats and proteins Promotes rises in blood glucose, fatty acids, and amino acids "Saves" glucose for brain Enhances vasoconstriction rise in blood pressure to quickly distribute nutrients to cells 13

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