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Chapter 49 Outline
TWO SYSTEMS REGULATE HOMEOSTASIS Nervous System Control Axons release neurotransmitters into synaptic cleft Neurotransmitters bind to receptor proteins on membrane of postsynaptic cell Endocrine Control Comprised of ductless endocrine organs fig 49.1 Cells secrete chemical messengers called hormones Hormones transmitted through circulatory system All cells exposed to hormones , only target cells respond Possess receptor proteins for particular hormone Example: epithelial cells in uterus respond to estradiol INTERACTIONS BETWEEN NEURAL AND ENDOCRINE REGULATION Secretory Activity of Endocrine Gland Often Controlled by Nervous System Include adrenal medulla, posterior pituitary and pineal glands Glands are derived from neural ectoderm Major Site for Neural Regulation Is the Anterior Pituitary Gland Hypothalamus controls hormonal secretions of anterior pituitary Anterior pituitary in turn regulates other endocrine glands Other Hormone Activity Is Independent of Neural Control Example: release of insulin by pancreas and aldosterone by adrenal cortex Stimulated by increases in blood concentrations of glucose and potassium respectively CHEMICAL MESSENGERS IN ENDOCRINE CONTROL Chemical Categories of Hormones Peptide hormones are chains of amino acids joined by peptide bonds fig 49.2a Includes insulin, all hormones released by anterior and posterior pituitary Some are glycoproteins: proteins connected to carbohydrates Follicle-stimulating hormone, luteinizing hormone Released by anterior pituitary, regulate gonads Steroid hormones fig 49.2b Lipids derived from cholesterol Sex steroids secreted by gonads; include androgens, estrogens, progestins Corticosteroids secreted by adrenal cortex; include cortisol, aldosterone Amino acid derivatives not otherwise related Catecholamines are derived from tyrosine Secreted by adrenal medulla Include epinephrine and norepinephrine Thyroxine from the thyroid gland is also derived from tyrosine Melatonin from the pineal gland is synthesized from tryptophan Some chemical messengers function as hormones and neurotransmitters Norepinephrine released in sympathetic division of autonomic nervous system Also a hormone produced by adrenal medulla Suggest that neural and endocrine control share evolutionary origin Endocrine, Paracrine and Autocrine Regulation Endocrine gland may function only to produce hormones Hormone secreting cells clustered in that gland Examples: pituitary, thyroid, adrenal glands fig 49.3 Endocrine glands may have non-endocrine functions Gonads also produce gametes Brain, stomach, liver, kidneys and heart also release minor hormones Paracrine regulators: intercellular regulatory molecules that exert very local effects Affect cells in vicinity of release Degrade too rapidly to effect more distant cells Example: endothelial cells release nitric oxide Relax surrounding smooth muscle Causes vasodilation Example: prostaglandins Autocrine regulation has extreme local effect Regulator molecule acts on same cell that secretes it Regulatory molecules control rate of own release Intrinsic regulation superimposed by extrinsic control fig 49.4 THE MECHANISM OF HORMONE ACTION Hormones That Enter Cells fig 49.5 Steroid hormones are lipid-soluble, diffuse through target cell plasma membrane Hormones bind to receptors Most bind to cytoplasmic receptors when in cytoplasm of target cell and complex moves into nucleus In others, receptor is in nucleus, hormone must enter first Complex binds to DNA in nucleus, initiates transcription of specific genes Resulting messenger RNA directs synthesis of proteins May be enzymes that alter metabolism of target cell Thyroxine is also lipid soluble and enters cytoplasm of target cells Has no effect of its own on target cell Cytoplasmic enzyme removes one iodine forming triiodothyronine (T3) T3 enters nucleus and binds to receptor protein Complex then stimulates production of messenger RNA Hormones That Do Not Enter Cells Polar molecules cannot cross plasma membrane of target cells Include peptide hormones, catecholamines, epinephrine, norepinephrine Bind to receptor molecules on outer surface of plasma membrane Triggers events within cell cytoplasm Uses intermediates called second messenger if hormone is first messenger fig 49.6 Binding is reversible and usually brief Dissociates from receptor after second messenger activated May be carried by blood to another target cell Eventually degraded by enzymes in the liver Second Messengers in Action: How Epinephrine Works Epinephrine binds to a- and฿-adrenergic receptors each activates a different system The cyclic AMP (adenosine monophosphate) second messenger system First system described in early 1960s Epinephrine binds to ฿-adrenergic receptors on liver cell membrane fig 49.7 Binding to receptor causes one G protein subunit to dissociate from other two Released subunit diffuses within plasma membrane Encounters adenylyl cyclase, normally inactive membrane-bound enzyme G protein subunit activates adenylyl cyclase Activated adenyl cyclase produces cAMP from ATP cAMP leaves inner surface of membrane, diffuses within cytoplasm Binds and activates protein kinase-A Protein kinase-A adds phosphate groups to specific cellular proteins Proteins phosphorylated by protein kinase-A vary by cell type Variation results in diverse effects of epinephrin on different tissues Liver cells: activates phosphorylase, converts glycogen to glucose fig 49.7 Cardiac muscle cells: activates proteins that cause heart to beat faster, harder The IP3/Ca++ second messenger system Epinephrine binds to a-adrenergic receptors Works through a different G protein Activates another membrane-bound enzyme, phospholipase C fig 49.8 Cleaves certain membrane phospholipids Produces second messenger inositol triphosphate (IP3) Diffuses from membrane into cytoplasm, binds to receptors on surface of endoplasmic reticulum ER accumulates Ca++ by actively transporting it out of cytoplasm Other pumps transport Ca++ from cytoplasm to extracellular fluid Very steep concentration gradient between cytoplasm and inside of ER Another steep gradient between cytoplasm and extracellular fluid IP3 binds to receptors on ER, stimulates it to release Ca++ Ca++ may also enter cytoplasm through opened membrane calcium channels Ca++ in cytoplasm binds to calmodulin, has regulatory functions like cAMP Calmodulin activates a different protein kinase to phosphorylate a different set of proteins Advantage of multiple second messenger systems Example: antagonistic actions of epinephrin and insulin on liver cells Epinephrine uses cAMP as second messenger to convert glycogen to glucose Insulin promotes conversion of glucose to glycogen Thus, insulin cannot use cAMP as second messenger Insulin may in part utilize IP3/Ca++ second messenger system THE MAJOR ENDOCRINE GLANDS AND THEIR HORMONES Endocrine System Composed of Ten Major Organs tbl 49.1 The Posterior Pituitary Gland Pituitary gland is located in brain, below the hypothalamus fig 49.9 Produces nine major hormones Composed of two independently functioning glands Posterior pituitary derived from outgrowth of brain, retains neural connections Anterior pituitary derived from outgrowth of epithelium lining mouth Secretions of the posterior pituitary Antidiuretic hormone (ADH) = vasopressin fig 49.10 Regulates kidney water retention Damage or alcohol causes excessive urination Oxytocin Peptide hormone composed of nine amino acids Stimulates contraction of smooth muscles around mammary glands Initiates milk release with suckling Stimulates uterine contraction during childbirth Both hormones synthesized inside neuron cells in hypothalamus Transported down axons to synapses in pituitary Stored in axon terminals Released into blood stream with nerve stimulus The Anterior Pituitary Gland Initially associated with growth disorders Surgical removal corrects acromegaly fig 49.11 Tumors cause gigantism fig 49.12 Gigantism caused by excessive secretion of growth hormone (GH) in growing child Causes acromegaly when skeletal growth plates are sealed in adults Deficiency in childhood causes pituitary dwarfism Pituitary actually synthesizes the hormones it secretes fig 49.13 Many stimulate growth of target organ, including other endocrine glands Are called tropic hormones Summary of hormones secreted by anterior pituitary Growth hormone (GH or somatotropin) Promotes growth directly Stimulates liver to secrete hormones that promote growth of muscle and bone Adrenocorticotropic hormone (ACTH or corticotropin) Stimulates adrenal gland to produce corticosteroid hormones Corticosteroid actions Regulate production of glucose from fat Regulate balance of sodium and potassium in the blood Contribute to non-reproductive male secondary sex characteristics Thyroid-stimulating hormone (TSH) Stimulates thyroid to produce thyroid hormone (thyroxin) Thyroxin stimulates oxidative respiration Luteinizing hormone (LH) Plays an important role in the female menstrual cycle Stimulates testes to produce testosterone Testosterone initiates, maintains secondary sex characteristics Follicle-stimulating hormone (FSH) Significant in the female menstrual cycle Stimulates cells in testes, regulates sperm development FSH and LH are both gonadotropins Prolactin (PRL): stimulates breasts to produce milk Melanocyte-stimulating hormone (MSH) Stimulates epidermal color changes in reptiles and amphibians No known function in mammals Hypothalamic control of anterior pituitary gland secretion Control is via hormones not nerve impulses Neurons in hypothalamus secrete releasing factors Carried by blood directly to anterior pituitary fig 49.14 Transported inside short blood vessels that connect two beds of capillaries One bed in hypothalamus, other in anterior pituitary Each releasing factor is specific for one tropic hormone Thyrotropin releasing hormone (TRH) stimulates release of TSH Corticotropin releasing hormone (CRH) stimulates release of ACTH Gonadotropin releasing hormone (GnRH) stimulates FSH and LH Also secretes hormones that inhibit release of certain anterior pituitary hormones Somatostatin inhibits secretion of GH Prolactin inhibiting hormone (PIH) inhibits secretion of prolactin Melanotropin inhibiting hormone (MIH) inhibits secretion of MSH Travel in blood from hypothalamus directly to anterior pituitary Negative feedback control of anterior pituitary gland secretions Hypothalamus no longer considered to be "master gland" Adrenal medulla and pancreas not controlled by this system Hypothalamus and anterior pituitary are themselves controlled by hormones End hormones feed back to regulate glands that control their release fig 49.15 Example: hormonal control of thyroid gland TRH stimulates anterior pituitary to secrete TSH TSH stimulates tyroid to release thyroxine Thyroxine acts on many target organs including Hypothalamus to inhibits TRH secretion Anterior pituitary to inhibit TRH secretion This is an example of negative feedback inhibition Example: insufficient dietary iodine Thyroid cannot produce thyroxine which contains iodine Blood thyroxine levels very low Less feedback inhibition to hypothalamus and anterior pituitary Causes increased secretion of TRH and TSH Stimulates thyroid to grow, but without iodine still no thyroxine Causes an enlarged thyroid, a goiter fig 49.16 The Thyroid Gland: A Metabolic Thermostat Located in front of the neck Produces thyroxine Stimulates oxidative respiration, helps set body's metabolic rate In children, promotes growth and stimulates maturation of nervous system Children with under active thyroids have stunted growth, mental retardation Condition called cretinism Can supplement with oral thyroxine Produces calcitonin If blood Ca++ is too high, calcitonin stimulates its uptake into bones Lowers its level in the blood fig 49.17 The Parathyroid Glands: Regulators of Blood Ca++ Levels Four small glands attached to thyroid Produces parathyroid hormone (PTH) One of two hormones absolutely essential for survival Synthesized and released when Ca++ levels in blood get low Ca++ required for muscle contraction Extreme low levels cause muscle spasms Cause osteoclasts to dissolve bone with subsequent Ca++ release fig 49.17 Reabsorbs calcium from urine Activates vitamin D to absorb Ca++ from intestine Vitamin D deficiency causes rickets, poor bone formation The Adrenal Glands: Two Glands in One Adrenal glands located above each kidney Composed of inner adrenal medulla Composed of outer adrenal cortex The adrenal medulla: emergency warning siren With stress medulla produces epinephrine and norepinephrine Stimulates alarm response similar to sympathetic division of autonomic nervous system, but more prolonged Responses: increased blood sugar, faster heartbeat, increased blood pressure, dilated blood vessels in skeletal muscles, increased blood flow to heart and lungs Extension of fight or flight response The adrenal cortex: homeostasis of glucose and Na+ Produces cortisol (hydrocortisone) Maintains glucose homeostasis, thus called glucocorticoids Stimulate breakdown of muscle proteins into amino acids, carried to liver Stimulates liver to produce enzymes to convert amino acids to glucose, gluconeogenesis Important during fasting Modulate some aspects of the immune response Reduces inflammation Produces aldosterone Acts on kidney to promote uptake of Na+ Na+ needed for nerve conduction, blood pressure Prevents excess loss of Na+ and thus water from the urine Loss of salt and water causes fall in blood pressure Promotes excretion of K+ in urine Second hormone necessary for survival The Pancreas: Regulating Energy Balance Located behind the stomach, connected to duodenum by pancreatic duct Also secretes bicarbonate ions and various digestive enzymes Though to be just exocrine until clusters of cells identified Called islets of Langerhans fig 49.18 Diabetes mellitus results from pancreas damage Insulin produced by islets of Langerhans Type I: lack insulin secreting cells Treated with insulin injections Insulin used to come from animals, Now use human insulin from genetically engineered bacteria Type II: too few receptors in target tissue Insulin levels normal or high Must control diet and exercise Islets produce two hormones, interact to regulate glucose fig 49.19 Eating increases blood glucose levels Beta cells produce insulin Insulin promotes cellular uptake of glucose Glucagon produced by islet alpha cells when glucose levels fall Acts antagonistically to insulin Promotes hydrolysis of glycogen in liver and fat in adipose tissue Other Endocrine Glands Ovaries and testes Produce sex hormones Estrogen, progesterone regulate menstrual cycle Testosterone promote protein synthesis Gastrointestinal tract: secretes hormones involved in food digestion Pineal gland fig 47.24 Secretes melatonin Function in humans not well understood May be involved in inhibition of reproductive system Called third eye, responds to light in fish, amphibians and reptiles Released in response to darkness, may be involved with daily biorhythms Implicated in mood disorders like winter depression Atrial natriuretic hormone (ANH) is a small peptide made in heart Stimulates kidney to excrete salt and water in urine Antagonistic to aldosterone Erythropoietin Secreted by kidneys Stimulates bone marrow to produce red blood cells Skin secretes vitamin D Vitamin D secreted into extracellular fluid, carried to intestine Intestine stimulates absorption of calcium
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