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Functional Organization of the Endocrine System
Chapter 17: Functional Organization of the Endocrine System Pg 586 AP2 Chapter 17
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Chapter 17 Outline General Characteristics of the Endocrine System
Chemical structure of hormones Control & secretion rate Transport & distribution in the body Metabolism & Excretion Interaction of hormones with their target tissue Classes of Receptors AP2 Chapter 17
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I. General Characteristics of the Endocrine System
AP2 Chapter 17
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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: Prod’d in small amounts by a collection of cells Secreted in interstitial spaces Enters the cardiovascular system where it is transported some distance 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
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I. General Char. of the Endocrine Syst.
Endocrine System Nervous System Regulate activities of structures in body but do so differently Intimate relationship btwn these 2 syst’s is now recognized 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 [ ] All or none potentials carried along axons can be described as frequency-modulated 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
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I. General Char. of the Endocrine Syst
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 Autocrine Paracrine Hormones Neurohormones (AKA hormone) NT/Neuromodulator Pheromone AP2 Chapter 17
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I. General Char. of the Endocrine Syst. Intercellular chemical signals
Autocrine Secreted by cells in a local area & influences the activity of the same cell type from which it was secreted Paracrine Prod’d by a wide variety of tissues & secreted into tissues spaces; usually has a localized effect on others Hormones Secreted into the blood by specialized cells; travels some distance to target tissues; influences specific activities I. General Char. of the Endocrine Syst. Intercellular chemical signals AP2 Chapter 17
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I. General Char. of the Endocrine Syst. Intercellular chemical signals
Neurohormones (AKA hormone) Produ’d by neurons but function as hormones NT/Neuromodulator Prod’d by neurons & secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells Pheromone Secreted into the environment; modifies the physiology and behavior of other individuals of the same species I. General Char. of the Endocrine Syst. Intercellular chemical signals AP2 Chapter 17
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II. Chemical Structure of Hormones
Pg 589 Table 17.2 (Examples listed) Figure 17.3 AP2 Chapter 17
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II. Chemical Structure of Hormones
Proteins Short sequences of aa’s called polypeptides Derivatives of aa’s Lipids Glycoproteins AP2 Chapter 17
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III. Control of Secretion Rate
AP2 Chapter 17
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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 III. Control of Secretion Rate Figure 17.7 AP2 Chapter 17
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III. Control of Secretion Rate 3 major patterns of regulation
Non-hormonal Regulation of hormone secretion Nervous System regulation of hormone secretion 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 D suddenly in response to stimulation D in a relatively constant cycle AP2 Chapter 17
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III. Control of Secretion Rate 3 major patterns of regulation
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
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III. Control of Secretion Rate 3 major patterns of regulation
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
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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
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IV. Transport & Distribution in the body
AP2 Chapter 17
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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 Lipid soluble and do not like the watery environment of the blood thus it must be bound to a transport protein Pg 594 Fig 17.9 AP2 Chapter 17
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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 Little Ceasars AP2 Chapter 17
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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 b. Water 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. 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 AP2 Chapter 17
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V. Metabolism & Excretion
AP2 Chapter 17
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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 Ways to lengthen 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 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 Half life- this regards rate instead of amount. @ 35 MPH the car will burn through the same amount of fuel per mile regardless of whether that car has 10 gallons or 2 gallons in its tank. AP2 Chapter 17
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V. Metabolism & Excretion 4 major ways to remove hormones from bld
Excreted into the urine by the kidney or the bile by the liver Metabolism Enzymatically degraded in the bld, liver, kidney, lungs, or target tissues Byproducts are excreted in the bile & urine Active Transport Actively transported into cells and used again later as a NT or hormone 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
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VI. Interactions of hormones with their target tissues
AP2 Chapter 17
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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
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VI. Interactions of hormones w/their target tissues
Taking advantage of hormone shape to make drugs 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: Chemical that will bind to a receptor but inhibits its action (antihistamine) AP2 Chapter 17
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VI. Interactions of hormones w/their target tissues
Response to Hormone Can be constant or variable. Rxns can decrease rapidly with time. One Explanation: Fatigue after prolonged stimulation of targeted cells AP2 Chapter 17
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VI. Interactions of hormones w/their target tissues
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 Up-regulation Periodic increases in sensitivity of some cells to hormones Results from an increase in rate of receptor molecule synthesis Figure Pg 596 AP2 Chapter 17
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VI. Interactions of hormones w/their target tissues Down-regulation continued
2 ways of down regulation 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 Increased rate of receptor degradation Receptor hormone complexes are sometimes degraded more quickly than the receptor alone AP2 Chapter 17
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VII. Classes of Receptors
2 Major Categories of Hormones 2 Major Categories of Receptors (Figure pg 597) AP2 Chapter 17
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VII Classes of Receptors A
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
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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 membrane & bind to Intracellular Receptors. These are receptors in the cytoplasm or even the nucleus of the cell Thus the hormone-receptor complex interacts with the DNA directly to prod. a response.
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VII. Classes of Receptors 2 Major Categories
Membrane Bound Receptors Intracellular Receptors AP2 Chapter 17
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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
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1. Receptors that activate G-proteins
These have 3 subunits: a, b, & g Called G-proteins because a binds to guanine nucleotides Result #1: Activated a-subunit can alter the activity of molecules inside the cell prod’ing cellular responses AP2 Chapter 17 Fig 7.14 pg 599
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1. Receptors that activate G-proteins
Result #2: Activated a-subunit can combine w/ion channels causing them to open & close Some ions or molecules can act as intracellular modulators Enter or are synthesized w/in the cell that regulate enz activity in the cell Fig 7.15 pg 600 AP2 Chapter 17
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1. Receptors that activate G-proteins
Fig 7.16 pg 601 Result #3: Activated a-subunit can also alter the activity of enz’s inside the cell AP2 Chapter 17
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1. Receptors that activate G-proteins
Result #4: Alter the [ ] of intracellular mediators other than Ca2+ & cAMP Fig 7.17 pg 602 AP2 Chapter 17
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VII. Classes of Receptors
Membrane Bound Receptors Receptors that activate G-proteins When the hormone separates from the receptor additional G-proteins are no longer activated Inactivation of a-subunit occurs when phosphate is removed from the GTP-leaving GDP with the a-subunit Then the subunits of the G-protein recombine AP2 Chapter 17
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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
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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 2nd 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
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2. Receptors that directly alter the activity of intracellular enzymes
Altered enzyme activity can: or the activity of intracellular mediator molecules Results in the phosphorylation of intracellular proteins Intracellular mediators (Phosphoylated proteins) activate processes that prod the response of the cell Fig 7.18 pg 602 AP2 Chapter 17
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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 Fig 7.19 pg 603 AP2 Chapter 17
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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 Fig 7.20 pg 604 AP2 Chapter 17
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VII. Classes of Receptors 2 Major Categories
Membrane Bound Receptors Intracellular Receptors AP2 Chapter 17
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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
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VII. Classes of Receptors
Fxns of receptor-hormone complex: Alter the activity of enz’s of the cell 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
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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 hormone-receptor complex degradation Fig 7.21 pg 605 AP2 Chapter 17
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VII. Classes of Receptors
Intracellular Receptors Fig 7.21 pg 605 AP2 Chapter 17
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