Chapter 11 – Endocrine PDF

Chapter 11 – Endocrine Figure 11.24 An Advanced Stage of Goiter  Learning Objectives To Understand: The glands involved The types of hormones The regulation/control of the hormones Hormone Structures and Synthesis Permissiveness and synthesis Diseases from over or under...

Chapter 11 – Endocrine Figure 11.24 An Advanced Stage of Goiter  Learning Objectives To Understand: The glands involved The types of hormones The regulation/control of the hormones Hormone Structures and Synthesis Permissiveness and synthesis Diseases from over or under production Figure 11.1 Comparison of Exocrine and Endocrine Gland Secretions 3 Figure 11.11 Inputs That Act Directly on Endocrine Gland Cells to Stimulate or Inhibit Hormone Secretion 4  Endocrine Glands 1. Ductless 2. Secrete hormones into the blood 3. Hormones are carried to target cells having receptors for those hormones. 4. Many organs secrete hormones other than those discussed in this chapter such as the heart, liver, kidneys, and adipose tissue. 5. Neurohormones are secreted by specialized cells of the hypothalamus 6. Hormones help regulate body metabolism, growth, and reproduction Figure 11.13 Pathways By Which the Nervous System Influences Hormone Secretion 6  Common Aspects of Neural and Endocrine Regulation 1. Hormones and neurotransmitters both interact with specific receptors. 2. Binding to a receptor causes a change within the cell. 3. There are mechanisms to turn off target cell activity; the signal is either removed or inactivated. 4. Neurotransmitters and hormones have many similarities 5. Some hormones can also be neurotransmitters in the CNS  Figure 11.15 Typical Sequential 1. Pattern of a Hypophysiotropic Hormone–Anterior Pituitary Gland Hormone--Third Endocrine Gland Portal Hormone Cascade 2. Blood 3. ENDO GLAND Target 4. Response 8 Figure 11.9 Possible Fates and Actions of a Hormone Following Its Secretion By an Endocrine Cell 9 Figure 11.2 Overview of Major Hormones and Sites of Production 10  What Makes a (Chemical a) Hormone? A hormone is a chemical signal (peptide or “chemical” Hormones are secreted by a cell or group of cells Hormones are secreted into the blood Secretion from a cell to ECF or external environment Hormones are transported to a distant target Transported by blood Growth factors act at short distance Hormones exert their effect at very low concentrations 1 gram (g) =1 g 1 milligram (mg) =0.001 g A grain of sugar weighs 0.000625 grams 1 microgram (µg) =0.000 001 g 1 nanogram (ng) =0.000 000 001 g =0.000 000 000 1 picogram (pg) 001g Hormone Half-life Hormone Concentration Priming Effects/Upregulation Desensitization and Downregulation  Hormone Classifications by Action 1. Polar hormones: water soluble a. Cannot pass through plasma membranes b. Must be injected if used as a drug c. Includes polypeptides, glycoproteins, catecholamines, norepinephrine, and epinephrine 2. Nonpolar: iNsoluble in water a. Often called lipophilic hormones b. Can enter target cells directly c. Include steroids, thyroid hormone, and melatonin d. Can be taken orally in pill form  Chemical Classification of Hormones 1. Amines, derived from tyrosine and tryptophan a. Examples: hormones from the adrenal medulla, thyroid, and pineal glands 2. Polypeptides and proteins a. Examples: antidiuretic hormone, insulin, and growth hormone Chemical Classification of Hormones 3. Glycoproteins are long polypeptides bound to a carbohydrate. a. Examples: follicle-stimulating and luteinizing hormones, EPO, 4. Steroids are lipids derived from cholesterol a. Examples: testosterone, estradiol, progesterone, cortisol b. Secreted by adrenal cortex and gonads Polypeptide and Glycoprotein Hormones TABLE 11.2 Examples of Polypeptide and Glycoprotein Hormones, steroids Hormone Structure Gland Primary Effects Antidiuretic 9 amino acids Posterior pituitary Water retention and hormone vasoconstriction Oxytocin 9 amino acids Posterior pituitary Uterine and mammary contraction Insulin 21 and 30 amino Beta cells in Cellular glucose uptake, acids (double chain) pancreatic islets lipogenesis, and glycogenesis Glucagon 29 amino acids Alpha cells in Hydrolysis of stored glycogen pancreatic islets and fat ACTH 39 amino acids Anterior pituitary Stimulation of adrenal cortex Parathyroid 84 amino acids Parathyroid Increase in blood Ca2+ hormone concentration FSH, LH, TSH Glycoproteins Anterior pituitary Stimulation of growth, development, and secretory activity of target glands Epo  Hormone Interactions Synergistic Effects (1+1 >2) Permissive Effects Antagonistic Effects Figure 11.10 The Ability of Thyroid Hormone to “Permit” Epinephrine-Induced Release of Fatty Acids From Adipose Tissue Cells 16  Figure 11.4 Typical Synthesis and Secretion of Peptide Hormones (a) Peptide hormone (b) Example of post-translational processing processing 17 Figure 11.6a Schematic Overview of Steps Involved in Steroid Synthesis (a) General events of steroid hormone synthesis and secretion 18 Biosynthetic Pathway for Steroid Hormones Figure 11.7 Section Through An Adrenal Gland Showing Both The Medulla And The Zones of the Cortex, as Well as the Hormones They Secrete 20 The Endocrine Gland Systems  Hypothalamus and Pituitary Gland 1. Hypothalamus a. Very important for maintaining homeostasis and regulating the autonomic system. Contains centers for: 1) Hunger/satiety and thirst 2) Regulation of body temperature 3) Regulation of sleep and wakefulness 4) Sexual arousal and performance 5) Emotions of fear, anger, pain, and pleasure 6) Control of the endocrine system 7) Controls hormone secretion from the pituitary gland Regions of the Hypothalamus Hypothalamus and Pituitary Gland b. Regions of the Hypothalamus and Functions 1) Lateral region: hunger 2) Medial region: satiety 3) Preoptic-anterior: shivering, hyperventilation, vasodilation, sweating 4) Supraoptic: produces antidiuretic hormone, which helps control urine formation 5) Paraventricular: produces the hormone oxytocin, which stimulates childbirth Hypothalamic Control of the Posterior Pituitary Major Endocrine Glands  Pituitary Gland 6 Hormones 2 Hormones Epithelial -----Neural Figure 11.14 Relation of the Pituitary Gland to the Brain and Hypothalamus and Neural and Vascular Connections Between the Hypothalamus and Pituitary Gland (a) Location of pituitary gland and hypothalamus (b) Hypothalamo-hypophyseal portal system 28  Figure 11.17 Hormone Secretion By the Anterior Pituitary Gland Is Controlled By Hypophysiotropic Hormones Released By Hypothalamic Neurons and Reaching the Anterior Pituitary Gland By Way of the Hypothalamo–Hypophyseal Portal Vessels 29  Pituitary Hormones 3. Posterior Pituitary Hormones a. Stores and releases two hormones made in the hypothalamus: 1) Antidiuretic hormone (ADH), which promotes the retention of water in the kidneys (also called arginine vasopressin – AVP) 2) Oxytocin, which stimulates contractions in childbirth and milk let-down in lactation Hypothalamus and Pituitary Gland c. Regulation of the Pituitary Gland 1) ADH and oxytocin are transported along the hypothalamo-hypophyseal tract to the posterior pituitary gland, where they are stored until needed. 2) The hypothalamus also produces releasing hormones and inhibiting hormones that are transported along the adenohypophysis to the anterior pituitary to regulate the secretion of pituitary hormones. ADH Oxytocin nine amino acid residues (nonapeptides) ADH 33 Hypothalamic Control of the Posterior Pituitary (1) 1. ADH and oxytocin are produced by the supraoptic and paraventricular nuclei of the hypothalamus, respectively 2. They are transported along axons of the hypothalamo-hypophyseal tract to the posterior pituitary where they are stored. 3. Release is controlled by neuroendocrine reflexes. a. ADH is stimulated by an increase in blood osmolality b. Oxytocin is stimulated by sucklings Homeostasis of Plasma Concentration Pituitary Gland- Anterior  Pituitary Hormones Secreted by the anterior lobe Trophic hormones stimulate hormone secretion in other glands: 1. Growth hormone (GH) 2. Thyroid-stimulating hormone (TSH) 3. Adrenocorticotropic hormone (ACTH) 4. Follicle-stimulating hormone (FSH) 5. Luteinizing hormone (LH) – in the male, it is interstitial cell stimulating hormone (ICSH) 6. Prolactin (PRL)  Anterior Pituitary Hormones 6 Hormones Anterior Pituitary (another view) 1. 2. 3. 1. 4. 5. 6. 39  (your text) Figure 11.16 Targets and Major Functions of the Six Classical Anterior Pituitary Gland Hormones 1 2 3 4 5 6 (the order and number do not matter!) 40 Hypothalamic Control of the Anterior Pituitary 1. The anterior pituitary is controlled via releasing and inhibiting hormones transported through the hypothalamo- hypophyseal portal system. Vascular Link Between the Hypothalamus and Anterior Pituitary Hypothalamic Control of the Anterior Pituitary 2. Releasing and inhibiting hormones a. Corticotropin-releasing hormone (CRH) b. Gonadotropin-releasing hormone (GRH) c. Prolactin-inhibiting hormone (PIH) (dopamine) d. Somatostatin (growth hormone-inhibiting hormone (GHIH) e. Thyrotropin-releasing hormone (TRH) f. Growth hormone−releasing hormone (GHRH)  Hypothalamic Control of the Anterior Pituitary TABLE 11.7 Hypothalamic Hormones Involved in the Control of the Anterior Pituitary Hypothalamic Hormone Structure Effect on Anterior Pituitary Corticotropin-releasing 41 amino acids Stimulates secretion of adrenocorticotropic hormone hormone (CRH) (ACTH) Gonadotropin-releasing 10 amino acids Stimulates secretion of follicle-stimulating hormone (FHS) hormone (GnRH) and luteinizing hormone (LH) Prolactin-inhibiting Catecholamine Inhibits prolactin secretion hormone (PIH): dopamine Somatostatin 14 amino acids Inhibits secretion of growth hormone Thyrotropin-releasing 3 amino acids Stimulates secretion of thyroid-stimulating hormone (TSH) hormone (TRH) Growth hormone-releasing 44 amino acids Stimulates growth hormone secretion hormone (GHRH) All but PIH are peptides Feedback Control of the Anterior Pituitary 1. The final product regulates secretion of pituitary hormones – negative feedback inhibition 2. The relationship between the hypothalamus, anterior pituitary, and the target tissue is called an axis 3. Inhibition can occur at the pituitary gland level, inhibiting response to hypothalamic hormones. 4. Inhibition can occur at the hypothalamus level, inhibiting secretion of releasing hormones. Feedback Control of the Anterior Pituitary  Higher Brain Controls 1. Since the hypothalamus receives input from higher brain regions, emotions can alter hormone secretion. a. At least 26 brain regions and olfactory neurons send axons to the GnRH-producing neurons. b. Stressors increase CRH production as part of the pituitary-adrenal axis c. Circadian rhythms Anterior Pituitary Hormones  Figure 11.21a Location of the Bilobed Thyroid Gland (a) Location of thyroid gland Located just below the larynx Has two lobes on either side of the trachea, connected by the isthmus 49  Thyroid Gland Structure 3. Microscopic Thyroid Gland Structure a. Consists of hollow spaces called thyroid follicles lined with simple cuboidal epithelium composed of follicular cells that produce thyroxine 4. Interior of the follicles is filled with a fluid called colloid. 5. Outside of the follicles are parafollicular cells that secrete calcitonin Production and Action of Thyroid Hormone 1. Thyroglobulin is made by the follicular cells. a. Thyroid follicles actively accumulate iodide (I-) and secrete it into the colloid. b. The iodine is attached to tyrosines within the thyroglobulin molecule. 1) One iodine produces monoiodotyrosine (MIT). 2) Two iodines produce diiodotyrosine (DIT). Thyroglobulin is the major component needed for synthesis of thyroxine and triiodothyronine. Regulation of Thyroid Hormone Secretion Production and Action of Thyroid Hormone c. Enzymes within the colloid attach MIT and DIT together: 1) DIT + DIT = T4 (tetraiodothyronine or thyroxine) 2) DIT + MIT = T3 (triiodothyronine) d. These are still bound to thyroglobulin. 1) They dissociate from thyroglobulin when the thyroid gland is stimulated by TSH. 2) Secreted into the blood Production and Storage of Thyroid Hormone Production and Action of Thyroid Hormone 2. Action of Thyroid Hormone a. Stimulates protein synthesis b. Promotes maturation of the nervous system c. Increases rates of cellular respiration d. Elevates basal metabolic rate Type I - TH + TH Type II MHC MHC Mitos Mitos Thyroid Hormone Action 1. Thyroxine (T4) travels to target cells on thyroxine-binding globulin (TBG). 2. Some T3 is also released, but is not bonded to a carrier; “free iodine” 3. Inside the target cell, T4 is converted to T3. 4. Receptor proteins are located inside the nucleus bound to DNA. 5.Receptor proteins are located inside the nucleus bound to DNA. The hormone response element on the DNA has two half-sites, one for a T3 receptor and one for a 9-cis-retinoic acid receptor (a Vit A derivative). 6.Binding of these molecules forms a heterodimer because there are two different receptors 7.The binding of T3 will cause corepressor proteins to be removed and coactivator proteins to be recruited. 8.Vitamin D action in the cell is similar. Thyroid Hormone Action  Diseases of the Thyroid 1. Iodine deficiency leads to overstimulation of the thyroid gland (no negative feedback on pituitary gland) and growth of a goiter. 2. It also leads to hypothyroidism: low metabolic rates, weight gain and lethargy, poor adaptation to cold stress, and myxedema (accumulation of fluids in subcutaneous connective tissues). 3. Grave’s Disease – hyperthyroidism 4. Cretinism results from hypothyroidism during pregnancy to about 6 months after birth  Comparison of Hyperthyroidism and Hypothyroidism TABLE 11.8 Comparison of Hypothyroidism and Hyperthyroidism Feature Hypothyroid Hyperthyroid Growth and development Impaired growth Accelerated growth Activity and sleep Lethargy; increased sleep Increased activity; decreased sleep Temperature tolerance Intolerance to cold Intolerance to heat Skin characteristics Coarse, dry skin Normal skin Perspiration Absent Excessive Pulse Slow Rapid Gastrointestinal Constipation; decreased Frequent bowel movements; symptoms appetite; increased weight increased appetite; decreased weight Reflexes Slow Rapid Psychological aspects Depression and apathy Nervous,“emotional” state Plasma T4 levels Decreased Increased Chemical Structures of the (Amine) THYROID Hormones 60 Feedback Control of the Anterior Pituitary How Iodine Deficiency Causes Goiter  Symptoms of Hyperthyroidism Graves’ disease is an autoimmune disorder in which autoantibodies bind to the receptors for TSH on thyroid gland follicular cells. This causes growth of the thyroid and stimulates the excessive secretion of thyroid hormones. Although TSH levels are very low because of negative feedback, the thyroid continues to be stimulated by the thyrotropin receptor antibodies to grow and secrete thyroxine. The hyperthyroidism produces such symptoms as sensitivity to heat, palpitations, and others. Many people with Graves’ disease also have Graves’ opthalmopathy, where anatomical changes in the orbit of the eyes produce bulging of the eyes, or exophthalmos. Graves’ disease is the most common cause of hyperthyroidism and is 5 to 10 times more common in women than in men. Anterior Pituitary Hormones Structure of the Adrenal Glands 1. Found atop the kidneys 2. Consist of an outer adrenal cortex and an inner adrenal medulla that function as separate glands a. The adrenal medulla is neural tissue and secretes epinephrine and norepinephrine in response to sympathetic neural stimulation. b. The adrenal cortex is glandular epithelium and secretes steroid hormones in response to ACTH; three layers – zona glomerulosa, zona fasciculata, and zona reticularis Anatomy of the Adrenal Glands Mineralocorticoids aldosterone Glucocorticoids Cortisol EPI, NOREP Metabolic Effects of Glucocorticoids  Functions of the Adrenal Cortex 1. Secretes hormones made from cholesterol; called corticosteroids or corticoids 2. Three categories: a. Mineralocorticoids from the zona glomerulosa regulate Na+ and K+ balance. 1) Example: aldosterone b. Glucocorticoids from the zona fasciculata regulate glucose metabolism. 1) Example: cortisol c. Adrenal androgens from the zona reticularis are weak sex hormones that supplement those made in the gonads. Example: DHEA.  Functions of the Adrenal Cortex 3. Functions of cortisol (hydrocortisone) a. Stimulates protein degradation b. Stimulates gluconeogenesis and inhibits glucose utilization to raise blood glucose levels c. Stimulates lipolysis 4. Exogenous glucocorticoids are used medically to suppress immune response and inhibit inflammation; can have many negative side effects Steroid Hormones of the Adrenal Cortex Figure 11.25 CRH-ACTH-Cortisol Pathway Figure 11.26 Patient with Florid Cushing’s Syndrome 71  Functions of the Adrenal Medulla 1. Epinephrine and Norepinephrine a. Activated with sympathetic response b. Have effects similar to sympathetic innervation but lasting 10 times longer c. Increase cardiac output, respiratory rate, and mental alertness; dilate coronary blood vessels; elevated metabolic rates  Functions of the Adrenal Gland 2. Stress and the Adrenal Gland a. Stress increases secretion of ACTH, which results in increased glucocorticoid release. b. The stress hormones are glucocorticoids, epinephrine, and CRH c. Called the general adaptation syndrome (GAS). 1) Good for proper recovery after stress, such as an illness or trauma. 2) Cortisol helps inhibit the immune system so it does not over respond. Functions of the Adrenal Gland d. Chronic stress leads to an increased risk of illness. 1) Cortisol may act on higher brain regions, contributing to depression and anxiety and memory. 2) By stimulating the liver to release glucose, insulin receptors may become resistant, making it harder to treat people with diabetes.  Cushing’s Syndrome Cushing’s syndrome results from chronically high levels of glucocorticoids It causes lipolysis and a redistribution of fat that can produce a “buffalo hump” (a fatty deposit between the shoulders and the below the back of the neck), a “moon” (round) face, and other symptoms. It most commonly occurs when a person takes sustained high doses of glucocorticoid medicines (prednisone, prednisolone, and dexamethasone), but it can be produced by either: a pituitary tumor that secretes excessive ACTH a benign tumor of the adrenal that secretes excessive cortisol without requiring ACTH stimulation Activation of Pituitary-Adrenal Axis by Nonspecific Stress Functions of the Adrenal Gland Stages of GAS 1) Alarm reaction – activates the adrenal glands 2) Stage of resistance – readjustments in response 3) Stage of exhaustion – may lead to sickness or death GAS effects 1) Stimulates growth of adrenal glands 2) Atrophy of lymphatic tissue of spleen, lymph nodes, and thymus 3) Formation of bleeding peptic ulcers  Exogenous Glucocorticoids Exogenous glucocorticoids—including prednisone, prednisolone, and dexamethasone—are used medically to: suppress the humoral and cell-mediated portions of the immune system suppress inflammation that may result from many causes treatment of asthma, autoimmune diseases, and to suppress the immune rejection of transplanted organs. Anterior Pituitary Hormones  The Gonads Estrogen Testosterone Progesterone Estrogens Androgens 10 nmol/L? 0 F Frequency 10 0.7 2.6 8.3 10.4 41.6 [Total T] nmol/l Figure 11.5 Structures of Representative Steroid Hormones T is in the blood as 1) Free 2) Bound to Albumin 3) Bound to Sex Globulin Binding Protein (SGBP) 81  General Genomic Hormone Concept E a/b T TRANSCIPTION. FACTOR ACTIVATION Anterior Pituitary Hormones Metabolic Effects of Growth Hormone Has both anabolic and catabolic actions Promotes: 1)Cellular uptake of amino acids for protein synthesis (anabolic) 2)Breakdown and release of fats from adipose tissue which reduces use of glucose for energy (catabolic) Figure 11.27 Anatomy of a Long Bone During Growth Figure 11.28 Relative Growth In Brain, Total- Body Height (a Measure of Long-Bone and Vertebral Growth), and Reproductive Organs 85 Figure 11.35 A Growth Hormone-Secreting Tumor Causes Features of Acromegaly and Gigantism By Direct GH Effects and By GH- Induced Increases in IGF-1 Figure 11.34 Appearance of an Individual with Gigantism and Acromegaly 86 Anterior Pituitary Hormones Milk Production Anterior Pituitary Hormones Summary TABLE 11.6 Anterior Pituitary Hormones Hormone Target Tissue Principal Actions Regulation of Secretion ACTH Adrenal cortex Stimulates secretion of Stimulated by CRH (corticotropin-releasing (adrenocorticotrop glucocorticoids hormone); inhibited by glucocorticoids ic hormone) TSH (thyroid- Thyroid gland Stimulates secretion of thyroid Stimulated by CRH (corticotropin-releasing stimulating hormones hormone); inhibited by glucocorticoids hormone) GH (growth Most tissue Promotes protein synthesis and Inhibited by somatostatin; stimulated by hormone) growth; lipolysis and increased growth hormone-releasing hormone blood glucose FSH (follicle Gonads Promotes gamete production and Stimulated by GnRH stimulating stimulates estrogen production in (gonadotropinreleasing hormone); inhibited hormone) females by sex steroids and inhibin PRL (prolactin) Mammary glands Promotes milk production in Inhibited by PIH (prolactin-inhibiting and other sex lactating females; additional hormone) accessory organs actions in other organs LH (luteinizing Gonads Stimulates sex hormone Stimulated by GnRH; inhibited by sex hormone) secretion; ovulation and corpus steroids luteum formation in females; stimulates testosterone secretion in males Pancreas and Other Endocrine Glands Pancreas 1. The pancreas is both an endocrine and an exocrine gland. 2. Endocrine cells are located in pancreatic islets (islets of Langerhans). a. Alpha cells: glucagon b. Beta cells: insulin  Pancreas GI 3. Insulin a. Primary hormone regulating plasma glucose concentration. b. Insulin is secreted by beta cells when blood glucose levels rise after a sugary or carbohydrate meal. c. Its purpose is to lower blood glucose levels to the “normal” range. d. Action of Insulin 1) Insulin binds to receptors on target cells. a) Vesicles with GLUT4 carrier proteins bind to membrane. b) Glucose diffuses through GLUT4 channels by facilitated diffusion c) Occurs in adipose tissue, skeletal muscle, and the liver. 2) Indirectly stimulates the enzyme glycogen synthase in liver and skeletal muscles to promote sugar storage 3) Stimulates adipose tissue to store fat Action of Insulin Insulin mediated Non-insulin mediated  Pancreas 4. Glucagon a. Antagonistic to insulin b. Secreted by alpha cells when blood glucose levels are low c. Purpose is to raise blood glucose levels to a “normal” range d. Action of Glucagon 1) Stimulates liver to hydrolyze glucagon into glucose and release it into the blood 2) Stimulates gluconeogenesis, conversion of noncarbohydrates into glucose 3) Stimulates lipolysis in adipose tissue so fat is released and used as a fuel source instead of glucose Glucose Homeostasis  Diabetes Mellitus Diabetes mellitus is characterized by fasting hyperglycemia and the presence of glucose in the urine. There are two major forms of this disease: Type 1 diabetes is caused by destruction of the beta cells and the resulting lack of insulin secretion. Type 2 diabetes is caused largely by insulin resistance, or decreased tissue sensitivity to the effects of insulin. Gestational diabetes occurs in about 4% of pregnancies due to insulin secretion that is inadequate to meet the increased demand imposed by the fetus and the anti- insulin effect of certain placental hormones.  Location Pineal gland Hypothalamus Posterior pituitary (N) Anterior pituitary Thyroid gland Parathyroid gland Thymus gland Heart (C) Liver (C) Stomach and small intestine (C) Pancreas (G) Adrenal cortex (G) Adrenal medulla (N) Kidney (C) Skin (C) Testes (male) (G) Ovaries (female) (G) Adipose tissue (C) KEY Placenta (pregnant G = gland C = endocrine cells females only) (C) N = neurons P = peptide  Figure 11.18 The Effects of Definitively Established Hypophysiotropic Hormones on the Anterior Pituitary Gland Major known hypophysiotropic hormones Major effect on anterior pituitary Corticotropin-releasing hormone (CRH) → Stimulates secretion of ACTH Thyrotropin-releasing hormone (TRH) → Stimulates secretion of TSH Growth hormone-releasing hormone (GHRH) → Stimulates secretion of GH Somatostatin (SST) → Inhibits secretion of GH Gonadotropin-releasing hormone (GnRH) → Stimulates secretion of LH and FSH Dopamine (DA)* → Inhibits secretion of prolactin *Dopamine is a catecholamine; all the other hypophysiotropic hormones are peptides. Evidence exists for PRL-releasing hormones, but they have not been unequivocally identified in humans. One possibility is that TRH may serve this role in addition to its actions on TSH. 98 Figure 11.19 Summary of the Hypothalamic-Anterior Pituitary Gland System 99  Hormone Transport in the Blood Most peptide and all catecholamine hormones are water- soluble. Therefore, with the exception of a few peptides, these hormones are transported simply dissolved in plasma. In contrast, the poorly soluble steroid hormones and thyroid hormones circulate in the blood largely bound to plasma proteins. Small concentrations, though, are dissolved in plasma (“free hormones”). Only free hormones interact with target cells. 100  Table 11.1 Categories of Hormones Chemical Class Major Form Location of Most Common Signaling Rate of in Plasma Receptors Mechanisms* Excretion/Metab olism Peptides and Free Plasma Second messengers (for Fast (minutes) catecholamines (unbound) membrane example, cAMP, Ca2+, IP3) Enzyme activation by receptor (for example, JAK) Intrinsic enzymatic activity of Read Ca2+ as Ca superscript two plus receptor (for example, tyrosine autophosphorylation) Steroids and Protein- Intracellular Intracellular receptors directly Slow (hours to thyroid hormone bound alter gene transcription days) 101  Regulation of Responsiveness to Hormones The ability of a cell to respond to a hormone depends upon the presence of specific receptors for that hormone on or in the target cell. An increase in the number of receptors for a hormone is called up-regulation. A decrease in the number of receptors for a hormone is called down-regulation. If a certain hormone must be present in order for another hormone to exert its full effect, this is called permissiveness. 102  Effects of Hormone-Receptor Binding Peptide and Catecholamine (Amine) Hormones: Bind to receptors on cell membrane. Activated receptors influence one of the following: – Enzyme activity that is part of receptor – Activity of JAK (janus) kinases associated with receptor – G-Proteins that are coupled to ion channels or enzymes, and activate secondary messengers ( cAMP, Ca2+ ) These hormones can exert rapid effects (enzymes) or delayed effects (transcription). Steroid and Thyroid Hormones: Bind to intracellular receptors; called “nuclear” receptors, whether they are found in the nucleus or cytoplasm This results in activation (or inhibition) of transcription of certain genes. 103  Pharmacological Effects of Hormones The administration of very large quantities of a hormone for medical purposes may have effects in an individual that are not usually observed at physiological concentrations. These pharmacological effects can also occur in diseases involving the secretion of excessive amounts of hormones. 104  Control by Other Hormones A hormone that controls the secretion of another hormone is often referred to as a tropic hormone. A hormone that controls secretion of another hormone and stimulates growth of the endocrine gland that secretes the second hormone is often called a trophic hormone. Example: Thyroid Stimulating Hormone (TSH) stimulates secretion of Thyroid Hormones from the thyroid gland, but also promotes growth of the thyroid gland. 105  Types of Endocrine Disorders Hyposecretion: the secretion of too little hormone Hypersecretion: the secretion of too much hormone Hyporesponsiveness: decreased responsiveness of the target cells to hormone Hyperresponsiveness: increased responsiveness of the target cells to hormone 106  Posterior Pituitary Hormones The posterior pituitary does not synthesize the two hormones that it secretes; they are produced in the hypothalamus. – Oxytocin is involved in the milk ejection reflex of lactation, uterine contractions during childbirth, and emotional bonding – Vasopressin (antidiuretic hormone) is involved in blood vessel constriction and in regulation of water balance and osmolarity. Control of posterior pituitary hormone secretion by the hypothalamus: – The hormones oxytocin and vasopressin are stored in the posterior pituitary gland. – Various stimuli cause action potentials in the hypothalamic neurons that secrete oxytocin and vasopressin; these action potentials trigger the release of the stored hormones. 107  Anterior Pituitary Gland Hormones and the Hypothalamus Certain nuclei of the hypothalamus secrete hormones that control secretion of all the anterior pituitary hormones. Hypothalamic hormones that regulate anterior pituitary function are called hypophysiotropic hormones or hypothalamic releasing or inhibiting hormones. Each hypophysiotropic hormones (with the exception of dopamine) is the first in a three-hormone sequence: – The hypophysiotropic hormone controls the secretion of an anterior pituitary hormone. – The anterior pituitary hormone controls the secretion of a hormone from another endocrine gland. – The hormone from the other endocrine gland is secreted and performs its function on its target cells. 108  Control of Hypophysiotropic Hormones Neural Control: The hypothalamus receives both stimulatory and inhibitory synaptic input from all areas of the CNS. Specific neural pathways influence secretion of each hypophysiotropic hormone. Many neurotransmitters are released at synapses of neurons that produce hypophysiotropic hormones. There is a strong circadian influence on secretion of certain hypophysiotropic hormones. Negative Feedback Control: A high level of the final hormone in a synthetic pathway slows down or stops its own production pathway, by inhibiting the secretion of the hypophysiotropic hormone and the anterior pituitary hormone. This keeps third hormone in a three-hormone sequence from building up to an excessive level. 109  Hormonal Influences on Growth Hormones most important for human growth: Growth hormone Insulin-like growth factors 1 and 2 T3 Insulin Sex hormones (testosterone, estradiol) Cortisol 110  Actions of Thyroid Hormones 1 Metabolic Actions of T3: T3 stimulates carbohydrate absorption from the small intestine and increases fatty acid release from adipocytes. + + ATP is consumed in cells by Na K -ATPases at a high rate due to T3 stimulation, and thus the cellular stores of ATP must be maintained by increased metabolism of fuels. This calorigenic action of T3 represents a significant fraction of the total heat produced each day in a typical person. This action is essential for body temperature homeostasis. 111  Actions of Thyroid Hormones 2 Permissive Actions of T3: Some of the actions of T3 are due to its permissive effects on the actions of catecholamines. T3 up-regulates beta-adrenergic receptors in many tissues, notably the heart and nervous system. It is not surprising that the symptoms of excess thyroid hormone concentration closely resemble some of the symptoms of excess epinephrine and norepinephrine (sympathetic nervous system activity). 112  Actions of Thyroid Hormones 3 Effects of T3 on Growth and Development: T3 is required for normal production of growth hormone in the anterior pituitary gland. T3 exerts many effects on the central nervous system during development, including the formation of axon terminals and the production of synapses, the growth of dendrites and dendritic extensions (called “spines”), and the formation of myelin. 113  Hypothyroidism and Hyperthyroidism Hypothyroidism: Any condition characterized by low thyroid hormone secretion Often due to iodine deficiency or loss of functional thyroid tissue Symptoms: Weight gain, cold sensitivity, lethargy, mental fatigue Most common form in the US is autoimmune thyroiditis (such as Hashimoto’s disease) Hyperthyroidism (Thyrotoxicosis): Any condition characterized by high thyroid hormone secretion Most common form in US is Graves’ disease (autoimmune) Can also be caused by a hormone-secreting tumor Symptoms: Heat sensitivity, weight loss, increased appetite, Increased heart rate, tremors, and nervousness Goiter: an enlargement of the thyroid gland, caused by an excess of TSH due to a thyroid hormone imbalance 114  Adrenal Hormones 1. Adrenal medulla: secretes catecholamines (epinephrine and norepinephrine) in response to sympathetic stimulation 2. Adrenal cortex: secretes mineralocorticoids (aldosterone) and glucocorticoids (cortisol) 3. Metabolic effects of catecholamines a. Similar to effects of glucagon 1) Stimulate glycogenolysis → release of glucose from liver 2) Lipolysis → release of fatty acids from adipose tissues b. Prepare body for increased energy demands in a fight/flight reaction  The Endocrine Response to Stress Stress, in its broadest meaning, is a real or perceived threat to homeostasis. These threats to homeostasis comprise a large number of situations, including physical trauma, prolonged exposure to cold, prolonged heavy exercise, infection, shock, decreased oxygen supply, sleep deprivation, pain, and emotional stresses. The endocrine system responds to stress by increasing the release of cortisol from the adrenal cortex and epinephrine from the adrenal medulla. 116  Physiological Functions of Cortisol Permits action of epinephrine and norepinephrine on smooth muscle cells surrounding blood vessels, which helps to control blood pressure Maintains cellular concentrations of metabolic enzymes required to produce glucose between meals, which helps to prevent low blood glucose concentrations. This is the reason cortisol is referred to as a glucocorticoid. Decreases events of the inflammatory response, such as capillary permeability and production of prostaglandins Allows for proper fetal development 117  Table 11.2 Effects of Increased Plasma Cortisol Concentration During Stress Effects on organic metabolism Stimulation of protein catabolism in bone, lymph, muscle, and elsewhere Stimulation of liver uptake of amino acids and their conversion to glucose (gluconeogenesis) Maintenance of plasma glucose concentrations Stimulation of triglyceride catabolism in adipose tissue, with release of glycerol and fatty acids into the blood Enhanced vascular reactivity (increased ability to maintain vasoconstriction in response to norepinephrine and other stimuli) Unidentified protective effects against the damaging influences of stress Inhibition of inflammation and specific immune responses Inhibition of nonessential functions (for example, reproduction and growth) 118  Adrenal Insufficiency 1 The general term for any situation in which plasma levels of cortisol are chronically lower than normal is adrenal insufficiency. Patients with adrenal insufficiency can experience a variety of symptoms, depending on the severity and cause of the disease, including weakness, fatigue, and loss of appetite and weight. Examination may reveal low blood pressure (in part because cortisol is needed to permit the full extent of the cardiovascular actions of epinephrine) and low blood sugar, especially after fasting (because of the loss of the normal metabolic actions of cortisol). 119  Adrenal Insufficiency 2 Primary adrenal insufficiency is due to a loss of adrenocortical function, as may rarely occur, for example, when infectious diseases such as tuberculosis infiltrate the adrenal glands and destroy them. The adrenals can also (rarely) be destroyed by invasive tumors. Most commonly by far, the syndrome is due to autoimmune attack causing the destruction of many of the cells of the adrenal glands. Because of this, all of the zones of the adrenal cortex are affected. Thus, not only cortisol but also aldosterone levels are decreased below normal in primary adrenal insufficiency. 120  Adrenal Insufficiency 3 This decrease in aldosterone concentration creates the additional problem of an imbalance in Na + ,K + , and water in the blood because aldosterone is a key regulator of those variables. The loss of salt and water balance may lead to hypotension (low blood pressure). Primary adrenal insufficiency from any of these causes is also known as Addison’s disease. 121  Cushing’s Syndrome 1 In Cushing’s syndrome, excess cortisol is present in the blood, even in the non-stressed person. The cause may be a primary defect (for example, a cortisol- secreting tumor of the adrenal) or may be secondary (usually due to an ACTH-secreting tumor of the anterior pituitary gland). In Cushing’s disease (secondary) the increased blood levels of cortisol promote uncontrolled catabolism of bone, muscle, skin, and other organs. 122  Cushing’s Syndrome 2 In Cushing’s syndrome problems include: – Osteoporosis – Muscles weakness – Thin, easily bruised skin – Blood sugar increases to levels observed in diabetes mellitus – Immunosuppression – Redistribution of fat (buffalo hump and moon face) – Hypertension (high blood pressure) Treatment of Cushing’s syndrome depends on the cause: – Surgical removal of the pituitary tumor – Adrenalectomy 123  Table 11.3 Actions of the Sympathetic Nervous System, Including Epinephrine Secreted by the Adrenal Medulla, During Stress Increased hepatic and muscle glycogenolysis (provides a quick source of glucose) Increased breakdown of adipose tissue triglyceride (provides a supply of glycerol for gluconeogenesis and of fatty acids for oxidation) Increased cardiac function (For Example, increased heart rate) Diversion of blood from viscera to skeletal muscles by means of vasoconstriction in the former beds and vasodilation in the latter Increased lung ventilation by stimulating brain breathing centers and dilating airways 124  Endocrine Control of Growth One of the major functions of the endocrine system is to control growth. At least a dozen hormones directly or indirectly have important functions in stimulating or inhibiting growth. Growth is also influenced by genetics and environmental factors, such as nutrition. Lack of sufficient amounts of protein, fatty acids, vitamins, or minerals interfere with growth. Growth involves cell division and protein synthesis, but height is determined by bone growth. 125  Table 11.4 Major Effects and Growth Hormone Promotes growth: Induces precursor cells in bone and other tissues to differentiate and secrete insulin-like growth factor 1 (IGF-1), which stimulates cell division. Also stimulates liver to secrete IGF-1. Stimulates protein synthesis, predominantly in muscle. Anti-insulin effects (particularly at high concentrations): Renders adipocytes more responsive to stimuli that induce breakdown of triglycerides, releasing fatty acids into the blood. Stimulates gluconeogenesis. Reduces the ability of insulin to stimulate glucose uptake by adipose and muscle cells, resulting in higher blood glucose concentrations. 126  Table 11.5 Major Hormones Influencing Growth Hormone Principal Actions Growth hormone Major stimulus of postnatal growth: induces precursor cells to differentiate and secrete insulin-like growth factor 1 (IGF-1), which stimulates cell division Stimulates liver to secrete IGF-1 Stimulates protein synthesis Insulin Stimulates fetal growth Stimulates postnatal growth by stimulating secretion of IGF-1 Stimulates protein synthesis Thyroid hormone Permissive for growth hormone’s secretion and actions Permissive for development of the central nervous system Testosterone Stimulates growth at puberty, in large part by stimulating the secretion of growth hormone Causes eventual epiphyseal closure Stimulates protein synthesis in male Estrogen Stimulates the secretion of growth hormone at puberty Causes eventual epiphyseal closure Cortisol Inhibits growth Stimulates protein catabolism 127 Table 11.6 Summary of Major Hormonal Influences on Bone Mass Hormones That Favor Bone Formation and Increased Bone Mass Insulin Growth hormone Insulin-like growth factor 1 (IGF-1) Estrogen Testosterone Calcitonin Hormones That Favor Increased Bone Resorption and Decreased Bone Mass Parathyroid hormone (chronic increases) Cortisol Thyroid hormone T3 128  Metabolic Bone Diseases 1 Rickets (in children) and osteomalacia (in adults) are conditions in which mineralization of bone matrix is deficient, causing the bones to be soft and easily fractured. A major cause of rickets and osteomalacia is deficiency of vitamin D. Osteoporosis is an imbalance between bone resorption and bone formation resulting in decreases in bone mass and strength. It leads to an increased fragility of bone and the incidence of fractures. Osteoporosis can occur in people who are immobilized, have an excessive plasma concentration of a hormone that favors bone resorption, or have a deficient plasma concentration of a hormone that favors bone formation. 129  Metabolic Bone Diseases 2 Osteoporosis is most commonly seen with aging. Everyone loses bone with age, but osteoporosis is more common in elderly women than men. The major reason for this is that menopause removes the antiresorptive effect of estrogen. Prevention is the focus of attention for osteoporosis. 130  Metabolic Bone Diseases 3 Treatment options for osteoporosis include: – treatment of postmenopausal women with estrogen or its synthetic analogs – a regular weight-bearing exercise program – adequate dietary Ca2+ and vitamin D intake – drugs, called bisphosphonates, that interfere with the resorption of bone by osteoclasts – other antiresorptive substances include calcitonin and selective estrogen receptor modulators (SERMs), which act by interacting with estrogen receptors, thereby compensating for the low estrogen after menopause 131  Clinical Case Study A 35-year-old man complained of chronic mouth pain and headaches. He noticed that his voice had deepened over the past few years, and he no longer wore his wedding ring because it was too tight. He also had loud snoring and sleep apnea. He was referred by his dentist to a physician, who noted the enlargement of the jaw and tongue as well as enlarged fingers and toes and a very deep voice. The patient’s blood pressure was elevated, as was his fasting plasma glucose concentration. His height and weight were in the normal ranges. The enlarged bones and facial features suggested acromegaly, which was confirmed by blood tests showing increased concentrations of growth hormone and IGF-1. An MRI scan revealed a 1.5 centimeters tumor of the anterior pituitary. If such a tumor had developed prior to puberty, the excess growth hormone secretion would have caused gigantism in the patient. How does a growth hormone-secreting tumor affect IGF-1 levels and produce the wide-ranging effects seen in this patient? How does acromegaly differ from gigantism? 132  The Endocrine System The endocrine system has same function as the nervous system: the control, integration and coordination of cell activities and organ function The nervous system functions rapidly and effects last for a short time, while the endocrine system functions more slowly, but the effects last longer. Endocrine Glands: ductless glands that secrete hormones into the body fluids Hormones: chemical messengers that are carried through the blood to their target cells Endocrine glands are distributed all over the body, and often are not anatomically connected Some endocrine glands secrete more than one hormone, and some hormones are produced by more than one gland Most often, in glands that secrete several hormones, different cell types produce different hormones. However, this is not always true. 133  Table 11.3 Actions of the Sympathetic Nervous System, Including Epinephrine Secreted by the Adrenal Medulla, During Stress Increased hepatic and muscle glycogenolysis (provides a quick source of glucose) Increased breakdown of adipose tissue triglyceride (provides a supply of glycerol for gluconeogenesis and of fatty acids for oxidation) Increased cardiac function (For Example, increased heart rate) Diversion of blood from viscera to skeletal muscles by means of vasoconstriction in the former beds and vasodilation in the latter Increased lung ventilation by stimulating brain breathing centers and dilating airways 134  Table 11.5 Major Hormones Influencing Growth Hormone Principal Actions Growth hormone Major stimulus of postnatal growth: induces precursor cells to differentiate and secrete insulin-like growth factor 1 (IGF-1), which stimulates cell division Stimulates liver to secrete IGF-1 Stimulates protein synthesis Insulin Stimulates fetal growth Stimulates postnatal growth by stimulating secretion of IGF-1 Stimulates protein synthesis Thyroid hormone Permissive for growth hormone’s secretion and actions Permissive for development of the central nervous system Testosterone Stimulates growth at puberty, in large part by stimulating the secretion of growth hormone Causes eventual epiphyseal closure Stimulates protein synthesis in male Estrogen Stimulates the secretion of growth hormone at puberty Causes eventual epiphyseal closure Cortisol Inhibits growth Stimulates protein catabolism 135  Comparison of Exocrine and Endocrine Glands Endocrine glands differ from exocrine glands in that: Endocrine glands secrete hormones that enter the interstitial fluid and diffuse directly into the blood. Exocrine glands secrete a variety of products into ducts, that lead to either the body surface (skin) or an internal lumen (intestines). 136  Hormone Structures and Synthesis Hormones fall into three major structural classes: – Amines – Peptides and proteins – Steroids 137  Hormone Transport in the Blood Most peptide and all catecholamine hormones are water- soluble. Therefore, with the exception of a few peptides, these hormones are transported simply dissolved in plasma. In contrast, the poorly soluble steroid hormones and thyroid hormones circulate in the blood largely bound to plasma proteins. Small concentrations, though, are dissolved in plasma (“free hormones”). Only free hormones interact with target cells. 138  Regulation of Responsiveness to Hormones The ability of a cell to respond to a hormone depends upon the presence of specific receptors for that hormone on or in the target cell. An increase in the number of receptors for a hormone is called up-regulation. A decrease in the number of receptors for a hormone is called down-regulation. If a certain hormone must be present in order for another hormone to exert its full effect, this is called permissiveness. 139  Effects of Hormone-Receptor Binding Peptide and Catecholamine (Amine) Hormones: Bind to receptors on cell membrane. Activated receptors influence one of the following: – Enzyme activity that is part of receptor – Activity of JAK (janus) kinases associated with receptor – G-Proteins that are coupled to ion channels or enzymes, and activate secondary messengers ( cAMP, Ca2+ ) These hormones can exert rapid effects (enzymes) or delayed effects (transcription). Steroid and Thyroid Hormones: Bind to intracellular receptors; called “nuclear” receptors, whether they are found in the nucleus or cytoplasm This results in activation (or inhibition) of transcription of certain genes. 140