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CHAPTER 16 Part A HUMAN ANATOMY AND PHYSIOLOGY II 1 CASE STUDY Chief Complaint: 8 year old girl with excessive thirst, frequent urination, and weight loss History: History: Cindy Mallon, an 8-year-old girl in previously good health, has noticed that, in the past month, she is increasingly thirsty. She gets up several times a night to urinate, and finds herself gulping down glassfulls of water. At the dinner table, she seems to be eating twice as much as she used to, yet she has lost 5 pounds in the past month. In the past three days, she has become nauseated, vomiting on three occasions, prompting a visit to her pediatrician. 2 CASE STUDY At the doctor's office, blood and urine samples are taken. The following lab results are noted: blood glucose level = 545 mg/dl (normal 50170 mg/dl) blood pH level = 7.23 (normally 7.35-7.45) urine = tested positive for glucose and ketone bodies (normally urine is free of glucose and ketone bodies) 3 THE DIABETES EPIDEMIC 4 ENDOCRINE SYSTEM: OVERVIEW Acts with nervous system to coordinate and integrate activity of body cells Influences metabolic activities via hormones transported in blood Response slower but longer lasting than nervous system Endocrinology Study of hormones and endocrine organs Slide 1 ENDOCRINE SYSTEM: OVERVIEW Controls and integrates Reproduction Growth and development Maintenance of electrolyte, water, and nutrient balance of blood Regulation of cellular metabolism and energy balance Mobilization of body defenses Slide 2 ENDOCRINE SYSTEM: OVERVIEW Exocrine glands Nonhormonal substances (sweat, saliva) Have ducts to carry secretion to membrane surface Endocrine glands Produce hormones Lack ducts Slide 3 ENDOCRINE SYSTEM: OVERVIEW Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands Hypothalamus is Neuroendocrine organ Some have exocrine and endocrine functions Pancreas, gonads, placenta Other tissues and organs that produce hormones Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart Slide 4 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) Slide 5 CHEMICAL MESSENGERS Hormones: long-distance chemical signals; travel in blood or lymph Autocrines: chemicals that exert effects on same cells that secrete them Paracrines: locally acting chemicals that affect cells other than those that secrete them Autocrines and paracrines are local chemical messengers; not considered part of endocrine system Slide 6 CHEMISTRY OF HORMONES Two main classes Amino acid-based hormones Amino acid derivatives, peptides, and proteins Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones Slide 7 MECHANISMS OF HORMONE ACTION Though hormones circulate systemically only cells with receptors for that hormone affected Target cells Tissues with receptors for specific hormone Hormones alter target cell activity Slide 8 MECHANISMS OF HORMONE ACTION Hormone action on target cells may be to 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 Slide 9 MECHANISMS OF HORMONE ACTION Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location 1. Water-soluble hormones (all amino acid–based hormones except thyroid hormone) Act on plasma membrane receptors Act via G protein second messengers Cannot enter cell Slide 10 MECHANISMS OF HORMONE ACTION 2. Lipid-soluble hormones (steroid and thyroid hormones) Act on intracellular receptors that directly activate genes Can enter cell Slide 11 PLASMA MEMBRANE RECEPTORS AND SECONDMESSENGER SYSTEMS cAMP signaling mechanism: 1. 2. 3. 4. 5. Hormone (first messenger) binds to receptor Receptor activates G protein G protein activates adenylate cyclase Adenylate cyclase converts ATP to cAMP (second messenger) cAMP activates protein kinases that phosphorylate proteins Slide 12 PLASMA MEMBRANE RECEPTORS AND SECONDMESSENGER SYSTEMS cAMP signaling mechanism Activated kinases phosphorylate various proteins, activating some and inactivating others cAMP is rapidly degraded by enzyme phosphodiesterase Intracellular enzymatic cascades have huge amplification effect Slide 13 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) Receptor 5 cAMP activates protein kinases. cAMP GTP GTP ATP GDP Inactive protein kinase GTP Active protein kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor activates G protein (Gs). 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 14 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. 1 Hormone (1st messenger) binds receptor. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger Extracellular fluid Receptor Cytoplasm Slide 15 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid G protein (Gs) Receptor GTP GDP GTP Cytoplasm 2 Receptor activates G protein (Gs). Slide 16 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Adenylate cyclase Extracellular fluid G protein (Gs) GTP Receptor GTP GDP GTP Cytoplasm 2 Receptor activates G protein (Gs). 3 G protein activates adenylate cyclase. Slide 17 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) cAMP GTP Receptor GTP ATP GDP GTP Cytoplasm 2 Receptor activates G protein (Gs). 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 18 FIGURE 16.2 CYCLIC AMP SECOND-MESSENGER MECHANISM OF WATER-SOLUBLE HORMONES. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) Receptor 5 cAMP activates protein kinases. cAMP GTP GTP ATP GDP Inactive protein kinase GTP Active protein kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor activates G protein (Gs). 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 19 PLASMA MEMBRANE RECEPTORS AND SECONDMESSENGER SYSTEMS PIP2-calcium signaling mechanism Involves G protein and membrane-bound effector – phospholipase C Phospholipase C splits PIP2 into two second messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3) DAG activates protein kinase; IP3 causes Ca2+ release Calcium ions act as second messenger PLASMA MEMBRANE RECEPTORS AND SECONDMESSENGER SYSTEMS Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin Calcium-bound calmodulin activates enzymes that amplify cellular response OTHER SIGNALING MECHANISMS Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones Some work without second messengers E.g., insulin receptor is tyrosine kinase enzyme that autophosphorylates upon insulin binding docking for relay proteins that trigger cell responses INTRACELLULAR RECEPTORS AND DIRECT GENE ACTIVATION Steroid hormones and thyroid hormone 1. 2. 3. 4. 5. Diffuse into target cells and bind with intracellular receptors Receptor-hormone complex enters nucleus; binds to specific region of DNA Prompts DNA transcription to produce mRNA mRNA directs protein synthesis Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus 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 mRNA 3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mRNA. 5 The mRNA directs protein synthesis. New protein FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus Receptorhormone complex 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Cytoplasm Receptor protein Nucleus 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. FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus 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. FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus Receptorhormone complex 2 The receptorhormone complex enters the nucleus. Receptor Binding region DNA mRNA 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. 3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mRNA. FIGURE 16.3 DIRECT GENE ACTIVATION MECHANISM OF LIPID-SOLUBLE HORMONES. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus 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 mRNA 3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mRNA. 5 The mRNA directs protein synthesis. New protein 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 Affinity of binding between receptor and hormone TARGET CELL ACTIVATION Hormones influence number of their receptors Up-regulation—target cells form more receptors in response to low hormone levels Down-regulation—target cells lose receptors in response to high hormone levels 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 HUMORAL STIMULI Changing blood levels of ions and nutrients directly stimulate secretion of hormones Example: Ca2+ in blood Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca2+ concentrations to rise and stimulus is removed Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+. Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Parathyroid glands Thyroid gland (posterior view) Parathyroid glands Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+. HORMONAL STIMULI Hormones stimulate other endocrine organs to release their hormones Hypothalamic hormones stimulate release of most anterior pituitary hormones Anterior pituitary hormones stimulate targets to secrete still more hormones Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from final target organs inhibit release of anterior pituitary hormones Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Adrenal Gonad cortex (Testis) Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones. Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Adrenal Gonad cortex (Testis) Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Adrenal Gonad cortex (Testis) Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Adrenal Gonad cortex (Testis) Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones. NEURAL STIMULI Nerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines Figure 16.4b Three types of endocrine gland stimuli. 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. Figure 16.4b Three types of endocrine gland stimuli. Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Figure 16.4b Three types of endocrine gland stimuli. 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. NERVOUS SYSTEM MODULATION Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms Example: under severe stress, hypothalamus and sympathetic nervous system activated body glucose levels rise Nervous system can override normal endocrine controls 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 Liver Half-life—time required for hormone's blood level to decrease by half Varies from fraction of minute to a week 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 INTERACTION OF HORMONES AT TARGET CELLS Multiple hormones may act on same target at same time Permissiveness: one hormone cannot exert its effects without another hormone being present Synergism: more than one hormone produces same effects on target cell amplification Antagonism: one or more hormones oppose(s) action of another hormone THE PITUITARY GLAND AND HYPOTHALAMUS Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe) Neural Anterior tissue pituitary (lobe) (adenohypophysis) Glandular tissue PITUITARY-HYPOTHALAMIC RELATIONSHIPS Posterior pituitary (lobe) Downgrowth of hypothalamic neural tissue Neural connection to hypothalamus (hypothalamichypophyseal tract) Nuclei of hypothalamus synthesize neurohormones oxytocin and antidiuretic hormone (ADH) Neurohormones are transported to and stored in posterior pituitary Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Supraoptic nucleus Inferior hypophyseal artery Axon terminals 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. Posterior lobe of pituitary Oxytocin ADH 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Axon terminals Posterior lobe of pituitary Supraoptic nucleus Inferior hypophyseal artery 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Axon terminals Posterior lobe of pituitary Supraoptic nucleus Inferior hypophyseal artery 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. Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Axon terminals Posterior lobe of pituitary Supraoptic nucleus Inferior hypophyseal artery 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. Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Supraoptic nucleus Inferior hypophyseal artery Axon terminals 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. Posterior lobe of pituitary Oxytocin ADH 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. PITUITARY-HYPOTHALAMIC RELATIONSHIPS Anterior Lobe: Originates as out-pocketing of oral mucosa Vascular connection to hypothalamus Hypophyseal portal system Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus Carries releasing and inhibiting hormones to anterior pituitary to regulate hormone secretion Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Hypothalamus 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 Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. 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 A portal system is two capillary plexuses (beds) connected by veins. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Hypothalamus Anterior lobe of pituitary Superior hypophyseal artery Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. 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 GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary A portal system is two capillary plexuses (beds) connected by veins. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Hypothalamus 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. GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. 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 A portal system is two capillary plexuses (beds) connected by veins. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Hypothalamus 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 Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. 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 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 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 ADH Diabetes insipidus ADH deficiency due to hypothalamus or posterior pituitary damage Must keep well-hydrated Syndrome of inappropriate ADH secretion (SIADH) Retention of fluid, headache, disorientation Fluid restriction; blood sodium level monitoring 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) 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) 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 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 Ghrelin (hunger hormone) also stimulates release HOMEOSTATIC IMBALANCES OF GROWTH HORMONE Hypersecretion In children results in gigantism In adults results in acromegaly Hyposecretion In children results in pituitary dwarfism Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Feedback Inhibits GHRH release Stimulates GHIH release Anterior pituitary Hypothalamus secretes growth hormone–releasing hormone (GHRH), and GHIH (somatostatin) Inhibits GH synthesis and release Growth hormone (GH) Indirect actions Direct actions (growthpromoting) (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 Figure 16.7 Disorders of pituitary growth hormone. 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 Thyroid hormones Target cells Stimulates Inhibits ADRENOCORTICOTROPIC HORMONE (CORTICOTROPIN) Secreted by corticotropic cells of anterior pituitary Stimulates adrenal cortex to release corticosteroids ADRENOCORTICOTROPIC HORMONE (CORTICOTROPIN) Regulation of ACTH release Triggered by hypothalamic corticotropin-releasing hormone (CRH) in daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can alter release of CRH GONADOTROPINS Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Secreted by gonadotrophs 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) PROLACTIN (PRL) Secreted by prolactin cells of anterior pituitary Stimulates milk production Role in males not well understood PROLACTIN (PRL) Regulation of PRL release Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine) Blood levels rise toward end of pregnancy Suckling stimulates PRL release and promotes continued milk production Hypersecretion causes inappropriate lactation, lack of menses, infertility in females, and impotence in males