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  AP BIOLOGY:
Chapter Forty-Nine 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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