Chapter 17: Functional Organization of the Endocrine System

Chapter 17: Functional Organization of the Endocrine System AP2 Chapter 17 Pg 586 1

Chapter 17 Outline I. General Characteristics of the Endocrine System II. Chemical structure of hormones III. Control & secretion rate IV. Transport & distribution in the body V. Metabolism & Excretion VI. Interaction of hormones with their target tissue VII. Classes of Receptors AP2 Chapter 17 2

I. General Characteristics of the Endocrine System AP2 Chapter 17 3

I. General Char. of the Endocrine Syst. Greek: Endo: within Krino: to secrete Hormone: to set in motion Endocrine System: Composed of endocrine glands that typically secrete chemical signals (a.k.a. hormones) into the cardiovascular system Exocrine glands secrete their products onto a surface Hormones are: a) Prod d in small amounts by a collection of cells b) Secreted in interstitial spaces c) Enters the cardiovascular system where it is transported some distance d) Acts on specific tissues (target tissues) at another site in the body to influence the activity of these tissues in some specific fashion AP2 Chapter 17 4

I. General Char. of the Endocrine Syst. Endocrine System Hormones can be described as Amplitude-modulated Signals & in [ ] of hormones in body fluids over periods ranging from minutes to hours Responses are also or based on [ ] Nervous System Regulate activities of structures in body but do so differently Intimate relationship btwn these 2 syst s is now recognized All or none potentials carried along axons can be described as frequencymodulated signals. These vary in frequency but not amplitude Low frequency weak stimulus High frequency strong stimulus FX last only 1 to a few milliseconds Local actions As always there are exceptions 5

I. General Char. of the Endocrine Syst. Intercellular chemical signals (Table 17.1 pg 588) allows 1 cell to communicate w/ another Coordinate & regulate the activities of most cells NT s & neuromodulators play essential roles in fxn of the NS Hormones are secreted by the Endocrine System 1. Autocrine 4. Neurohormones (AKA hormone) 2. Paracrine 3. Hormones 5. NT/Neuromodulator 6. Pheromone AP2 Chapter 17 6

I. General Char. of the Endocrine Syst. Intercellular chemical signals 1. Autocrine Secreted by cells in a local area & influences the activity of the same cell type from which it was secreted 2. Paracrine Prod d by a wide variety of tissues & secreted into tissues spaces; usually has a localized effect on others 3. Hormones Secreted into the blood by specialized cells; travels some distance to target tissues; influences specific activities AP2 Chapter 17 7

I. General Char. of the Endocrine Syst. Intercellular chemical signals 4. Neurohormones (AKA hormone) Produ d by neurons but function as hormones 5. NT/Neuromodulator Prod d by neurons & secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells 6. Pheromone Secreted into the environment; modifies the physiology and behavior of other individuals of the same species AP2 Chapter 17 8

II. Chemical Structure of Hormones Pg 589 Table 17.2 (Examples listed) Figure 17.3 AP2 Chapter 17 9

II. Chemical Structure of Hormones A. Proteins B. Short sequences of aa s called polypeptides C. Derivatives of aa s D. Lipids E. Glycoproteins AP2 Chapter 17 10

III. Control of Secretion Rate AP2 Chapter 17 11

III. Control of Secretion Rate Negative Feedback loops are used to help maintain the body in a state of homeostasis Positive Feedback loops is also used in a very limited capacity Figure 17.7 AP2 Chapter 17 12

III. Control of Secretion Rate 3 major patterns of regulation 1. Non-hormonal Regulation of hormone secretion 2. Nervous System regulation of hormone secretion 3. Hormonal regulation of hormone secretion As with everything in the body, it can be much more complicated involving multiple mechanisms Some hormones: Are in circulatory system at relatively constant levels Δ suddenly in response to stimulation Δ in a relatively constant cycle AP2 Chapter 17 13

III. Control of Secretion Rate 3 major patterns of regulation 1. Non-hormonal Regulation of hormone secretion Changes in the extracellular [ ] of a substance other than a hormone effect the function of the endocrine gland AP2 Chapter 17 14

III. Control of Secretion Rate 3 major patterns of regulation 1. Neural Control of the endocrine gland Neuron is synapsed with an endocrine gland and the neuron influences the activity of the gland AP2 Chapter 17 15

III. Control of Secretion Rate 3 major patterns of regulation 3. Hormonal regulation of hormone secretion Control of the secretory activity of one gland by a hormone or neurohormone secreted by another gland. AP2 Chapter 17 16

IV. Transport & Distribution in the body AP2 Chapter 17 17

IV. Transport & Distribution in the body 2 main ways to transport hormones in the blood 1. Unbound Hormones 2. Bound Hormones Water soluble and travel in the blood Pg 594 Fig 17.9 Lipid soluble and do not like the watery environment of the blood thus it must be bound to a transport protein AP2 Chapter 17 18

IV. Transport & Distribution in the body 2. Bound Hormones These are bound in a reversible fashion Equilibrium is established btwn bound and their unbound counterparts Bound are also trapped within the confines of the capillary because they are to big to filter thru These serve as a reservoir. Thus when one in tissue is used there are replacements that only need to be released from the blood stream These can also remain in the blood longer without being destroyed AP2 Chapter 17 19

IV. Transport & Distribution in the body Hormones go thru the bld & thus distributed quickly throughout the body They diffuse thru the capillary wall & enter interstitial spaces and the rate of that movement varies by hormone a. Lipid soluble hormones Pass thru capillary walls readily Typically travel bound to binding proteins Binding prevents their rapid diffusion from the circulatory system into the tissues Reservoir also gives a relatively constant rate of diffusion of the unbound hormone from circ.systm. AP2 Chapter 17 b. Water soluble hormones Must go thru the pores of the capillary walls (fenestrae) The capillaries of the organs regulated by and glands secreting these hormones usually have these large pores. These usually get into tissue at a slow rate 20

V. Metabolism & Excretion AP2 Chapter 17 21

V. Metabolism & Excretion Destruction & elimination of hormones limit the time that they are active in the body. The body s activities can or dependent on how long the hormone remains in the body Half-Life Length of time it takes for ½ the dose of a substance to be eliminated from the circulatory system. (RATE) Time to eliminate entire amount isn t helpful b/c it all depends on what you start with. Times vary dependent on specific hormone Ways to lengthen half-life Binding them to binding proteins Their structures may also protect the hormone Example Glycoproteins: their carb component protects them from proteolytic enzymes in circulatory system AP2 Chapter 17 22

V. Metabolism & Excretion 4 major ways to remove hormones from bld 1. Excretion Excreted into the urine by the kidney or the bile by the liver 2. Metabolism Enzymatically degraded in the bld, liver, kidney, lungs, or target tissues Byproducts are excreted in the bile & urine 3. Active Transport Actively transported into cells and used again later as a NT or hormone 4. Conjugation Substances are attached to hormones primarily in the liver. These normally make the hormone less active & increase its rate of excretion AP2 Chapter 17 23

VI. Interactions of hormones with their target tissues AP2 Chapter 17 24

VI. Interactions of hormones w/their target tissues Hormones (a.k.a. Ligands) Bind to receptors (proteins or glycoproteins) Bind at the receptor site (binding site) Binding Site: Chemical characteristics of the site allow only a specific type of chemical signal to bond to it Specificity can t get growth hormone to bind to insulin site Hormone receptors have a high affinity for the hormones that bind them, thus only a small [ ] results in a significant # of receptors being bound Presence or absence of receptor determines wh/cells will react to the hormone s release, thus it can travel throughout the body, but will only activate the proper cells 25

VI. Interactions of hormones w/their target tissues Drugs can be designed to have a similar structure to a natural hormone & may compete for the receptor s binding site Agonist: Chemical that will bond to a receptor & activate it (Histamine) Antagonist: Taking advantage of hormone shape to make drugs Chemical that will bind to a receptor but inhibits its action (antihistamine) AP2 Chapter 17 26

VI. Interactions of hormones w/their target tissues Can be constant or variable. Rxns can decrease rapidly with time. One Explanation: Response to Hormone Fatigue after prolonged stimulation of targeted cells AP2 Chapter 17 27

VI. Interactions of hormones w/their target tissues 1. Down-regulation # of receptors can also decrease over time after exposure Tissues that down regulate are usually designed to respond to short term hormone increases Tissues that respond to constant levels of hormones do not exhibit down-regulation 2. Up-regulation Periodic increases in sensitivity of some cells to hormones Results from an increase in rate of receptor molecule synthesis Figure 17.12 Pg 596 AP2 Chapter 17 28

VI. Interactions of hormones w/their target tissues Down-regulation continued 2 ways of down regulation 1. Synthesis rate of the receptor are reduced Most hormone receptor complexes are degraded over time. If they are not replaced because of no synthesis the ultimate result is less cell surface receptors 2. Increased rate of receptor degradation Receptor hormone complexes are sometimes degraded more quickly than the receptor alone AP2 Chapter 17 29

VII. Classes of Receptors 2 Major Categories of Hormones 2 Major Categories of Receptors (Figure 17.13 pg 597) AP2 Chapter 17 30

VII Classes of Receptors A. Hormones that bind to membrane bound receptors Include large molecules & water soluble molecules both can t pass thru the plasma membrane Examples: Proteins, glycoproteins, polypeptides, smaller molecules (epi/norepi) When the receptor is bound it initiates a response inside the cell Thus they interact w/the outside of the cell with membrane bound receptors Transmembrane receptors w/their receptor sites exposed to the outer surface of the plasma membrane AP2 Chapter 17 31

VII Classes of Receptors B. Hormones that bind intracellular receptors These include lipid-soluble and relatively small hormones. Examples: Thyroid hormones, steroid hormones (testosterone, estrogen, progesterone, aldosterone, & cortisol) Diffuse thru the plasma Thus the hormonereceptor complex interacts membrane & bind to Intracellular Receptors. with the DNA directly to These are receptors in the prod. a response. cytoplasm or even the nucleus of the cell 32

VII. Classes of Receptors 2 Major Categories Membrane Bound Receptors Intracellular Receptors AP2 Chapter 17 33

VII. Classes of Receptors Membrane Bound Receptors 2 major categories Mechanisms for membrane bound receptors 1. Receptors that activate G-proteins 2. Receptors that directly alter the activity of intracellular enzymes AP2 Chapter 17 34

1. Receptors that activate G-proteins AP2 Chapter 17 35 Fig 7.14 pg 599

1. Receptors that activate G-proteins Fig 7.15 pg 600 AP2 Chapter 17 36

1. Receptors that activate G-proteins Fig 7.16 pg 601 AP2 Chapter 17 37

1. Receptors that activate G-proteins Fig 7.17 pg 602 AP2 Chapter 17 38

VII. Classes of Receptors Membrane Bound Receptors 1. Receptors that activate G-proteins When the hormone separates from the receptor additional G-proteins are no longer activated Inactivation of α-subunit occurs when phosphate is removed from the GTP-leaving GDP with the α-subunit Then the subunits of the G-protein recombine AP2 Chapter 17 39

VII. Classes of Receptors Membrane Bound Receptors 2 major categories Mechanisms for membrane bound receptors 1. Receptors that activate G-proteins 2. Receptors that directly alter the activity of intracellular enzymes AP2 Chapter 17 40

2. Receptors that directly alter the activity of intracellular enzymes These receptor when bound directly alter the activity of an intracellular enzymes (mediators) w/no 2 nd messenger needed Altered enz s can be membrane bound or not Mediator enz s act as chemical signals that move from where they are altered into the cytoplasm where they activate processes that prod a cellular response Fig 7.18 pg 602 AP2 Chapter 17 41

2. Receptors that directly alter the activity of intracellular enzymes Altered enzyme activity can: a) or the activity of intracellular mediator molecules b) Results in the phosphorylation of intracellular proteins c) Intracellular mediators (Phosphoylated proteins) activate processes that prod the response of the cell Fig 7.18 pg 602 AP2 Chapter 17 42

2. Receptors that directly alter the activity of intracellular enzymes Some are bound & a portion of the receptor on the inner surface of the membrane acts as a phosphorylase enzyme that phosphorylates several specific proteins Phosphorylated proteins: Can be part of the membrane bound protein or not Influence the activity of other enzymes in the cell AP2 Chapter 17 Fig 7.19 pg 603 43

2. Receptors that directly alter the activity of intracellular enzymes Cascade Effect Most hormones act exponentially causing a pyramid effect that result in rapid responses Few mediator molecules activate several enz s & each enz activates several other enz s that prod a response An amplification system exists in wh/a few molecules can control the activity of many enz s w/in the cell AP2 Chapter 17 Fig 7.20 pg 604 44

VII. Classes of Receptors 2 Major Categories Membrane Bound Receptors Intracellular Receptors AP2 Chapter 17 45

VII. Classes of Receptors Lipid soluble hormones cross the plasma membrane into the cytoplasm or nucleus & bind to intracellular receptors by the process of diffusion Thus receptor location is in the cytoplasm or nucleus Fig 7.21 pg 605 AP2 Chapter 17 46

VII. Classes of Receptors Fxns of receptorhormone complex: a. Alter the activity of enz s of the cell b. Bind to DNA to prod a response: Via gene expression DNA is transcribed into mrna then translated into a protein Thus it increases the synthesis of a specific protein. Fig 7.21 pg 605 AP2 Chapter 17 47

VII. Classes of Receptors These types of rxns are not instant, they usually take several hours btwn hormone release & response is observed To make mrna & protein Hormone influence is limited via hormonereceptor complex degradation Fig 7.21 pg 605 AP2 Chapter 17 48

VII. Classes of Receptors Intracellular Receptors Fig 7.21 pg 605 AP2 Chapter 17 49