17-1 Endocrine System

17-2 I. Introduction to endocrine system A. Classes of Chemical Messengers –1. Autocrine chemical messengers: released by cells and have a local effect on same cell type from which chemical signals released; e.g., prostaglandin –2. Paracrine chemical messengers: released by cells and affect other cell types locally without being transported in blood; e.g., somatostatin –3. Neurotransmitter: produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells; e.g., acetylcholine. –4. Endocrine chemical messengers: type of intercellular signal. Produced by cells of endocrine glands, enter circulatory system, and affect distant cells; e.g., estrogen

17-3

17-4 B. Characteristics of the Endocrine System 1. Glands that secrete chemical messengers (hormones) into circulatory system 2. Hormone characteristics –Produced in small quantities –Secreted into intercellular space –Transported some distance in circulatory system –Acts on target tissues elsewhere in body 3. Regulate activities of body structures

17-5 C. Comparison of Nervous and Endocrine Systems Similarities 1.Both systems associated with the brain Hypothalamus Epithalamus 2.May use same chemical messenger as neurotransmitter and hormone. Epinephrine 3.Two systems are cooperative Nervous system secretes neuroendocrine peptides, or neurohormones, into circulatory system Some parts of endocrine system innervated directly by nervous system

17-6 Differences 1.Mode of transport –Axon –Blood 2.Speed of response –Nervous – instant/milliseconds –Endocrine – delayed/seconds 3.Duration of response –Nervous – milliseconds/seconds –Endocrine – minutes/days 4.Amplitude vs. frequency

17-7 A. Stability 1. Half-life: The length of time it takes for half a dose of substance to be eliminated from circulatory system 2. Long half-life: regulate activities that remain at a constant rate through time. Usually lipid soluble and travel in plasma attached to proteins 3. Short half-life: water-soluble hormones as proteins, epinephrine, norepinephrine. Have a rapid onset and short duration B. Communication 1. Interaction with target cell 2. Lipid soluble hormones pass through cell membrane and usually travel to nucleus 3. Water soluble hormones generally attach to a receptor site on cell membrane C. Distribution 1. Hormones dissolve in blood plasma and are transported in unbound or are reversibly bound to plasma proteins. 2. Hormones are distributed quickly because they circulate in the blood. II. General characteristics of hormones

D. Lipid soluble hormones 1. must connect to binding proteins in blood or would be catabolized quickly 2. long half lives as they are protected 3. tend to have more constant blood levels and regulate basal activity 3. the liver can attach water soluble radicals to these enzymes so that the kidneys can excrete the hormone 4. process called conjugation 17-8

17-9 E. Water soluble hormones 1. travel freely in circulatory system 2. larger and don’t diffuse through membranes easily 3. fenestrated target tissues 4. short half lives due to proteases circulating in blood 5. concentrations tend to change rapidly and they regulate activities with rapid onset and short duration

17-10

17-11

17-12 III. Patterns of Hormone Secretion A. Chronic hormone regulation. 1. Maintenance of relatively constant concentration of hormone. Thyroid hormone. B. Acute hormone regulation. Epinephrine in response to stress. C. Episodic (Cyclic) hormone regulation. Female reproductive hormones.

17-13 IV. Control of Hormone Secretion Most hormones controlled by negative feedback systems In negative feedback, the eventual product turns off the sensor which initiated the products synthesis-self limiting Common example is the heating of your house In positive feedback, the product stimulates the sensor to increase its own production-self propagating Most hormones are not secreted at constant rate, but their secretion is stimulated by three different methods 1.The action of a substance other than a hormone on an endocrine gland-humoral control-pth and Ca ion 2.Neural control of endocrine gland-ie adrenal cortex 3.Control of secretory activity of one endocrine gland by hormone or neurohormone secreted by another endocrine gland-pituitary gland and thyroid

17-14 Control by Humoral Stimuli

17-15 Control by Neural Stimuli

17-16 Control by Hormonal Stimuli

Hormone Receptors and Mechanisms of Action

17-18 V. Target Tissue Specificity and Response A. Portion of molecule where hormone binds is called binding site. B. If the molecule is a receptor (like in a cell membrane) the binding site is called a receptor site C. hormone/receptor site is specific; e.g., epinephrine cannot bind to the receptor site for insulin. D. The purpose of binding to target tissue is to elicit a response by the target cell. E. Diagram shows what happens with larger water soluble hormone which binds to a receptor on the membrane surface

17-19 F. Changes in Receptor Number 1. Normally, receptor molecules are degraded and replaced on a regular basis. 2. Down-regulation –Rate at which receptors are synthesized decreases in some cells after the cells are exposed to a hormone. –Combination of hormones and receptors can increase the rate at which receptor molecules are degraded. This combined form is taken into the cell by phagocytosis and then broken down. –Explains the desensitization that can occur to some drugs

Increase in Receptor Number- Up regulation –Some stimulus causes increase in synthesis of receptors for a hormone, thus increases sensitivity to that hormone –For example, FSH stimulation of the ovary causes an increase of LH receptors. –Prepares the ovarian cells’ membranes to prepare for the LH surge that stimulates ovulation

17-21 VI. Classes of Receptors A. Lipid soluble hormones 1. Lipid-soluble hormones bind to nuclear receptors 2. Lipid soluble hormones are relatively small molecules; pass through the plasma membrane 3. React either with enzymes in the cytoplasm or with DNA to cause transcription and translation 4. Examples include thyroid hormones, testosterone, estrogen, progesterone, aldosterone, and cortisol 5. because of transcription and translation processes, there is a lag time between hormone binding and having its effect exerted

B. Water-soluble hormones 1. Water-soluble hormones bind to membrane-bound receptors 2. integral proteins with receptor site at extracellular surface. 3. Interact with hormones that cannot pass through the plasma membrane. 4. Attachment of hormone causes intracellular reaction 5. often binding of hormone causes the production of a second molecule that activates existing internal systems 6. adrenalin acts this way 7. faster acting and shorter lived affects when compared to lipid soluble hormones 17-22

17-23

17-24 Action of Nuclear Receptors Proteins in cytoplasm or nucleus Hormones bind with intracellular receptor and receptor-hormone complex activate certain genes, causes transcription of mRNA and translation. These proteins (enzymes) produce the response of the target cell to the hormone Latent period of several hours because time is required to produce mRNA and protein Processes limited by breakdown of receptor- hormone complex Estrogen and testosterone produce different proteins in cells that cause the differing secondary sexual characteristics of females and males.

17-25

17-26 Membrane-Bound Receptors Intracellular mediators: ions or molecules that enter cell or are produced in cell Can be produced because of G protein activation Regulate intracellular enzyme activities

17-27

17-28 Insert table 17.5

17-29 Receptors that Activate G Proteins

17-30 G Proteins that open Calcium ion Channels

17-31 G Proteins that Interact with Adenylate Cyclase

17-32 G Proteins that Interact with other Intercellular Mediators

17-33 Receptors That Directly Alter the Activity of Intracellular Mediator

17-34 Receptors That Phosphorylate Intracellular Proteins Hormones bind to membrane-bound receptors. Part of receptor protein on inside of membrane acts as an enzyme to phosphorylate proteins E.g., insulin receptors bound to insulin cause phosphorylation of proteins and cell responds to presence of insulin.

17-35 Signal Amplification

17-36