1. PowerPoint ® Lecture Slides prepared by Janice Meeking, Mount Royal College C H A P T E R Copyright © 2010 Pearson Education, Inc. 16 The Endocrine System: Part A

2. Copyright © 2010 Pearson Education, Inc. The term hormone is derived from a Greek verb meaning – to excite or arouse Hormone is a chemical messenger that is released in one tissue (endocrine tissue/gland) and transported in the bloodstream to reach specific cells in other tissues Regulate the metabolic function of other cells Have lag times ranging from seconds to hours Tend to have prolonged effects Hormone actions must be terminated – how?

3. Copyright © 2010 Pearson Education, Inc. Intercellular communication types Autocrine - the cell signals itself through a chemical that it synthesizes and then responds to. Autocrine signaling can occur: solely within the cytoplasm of the cell or by a secreted chemical interacting with receptors on the surface of the same cell Paracrine - chemical signals that diffuse into the area and interact with receptors on nearby cells (cells within the same tissue). Endocrine - the chemicals are secreted into the blood and carried by blood and tissue fluids to the cells they act upon. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Hormones.html

4. Copyright © 2010 Pearson Education, Inc. Bloodstream

5. Copyright © 2010 Pearson Education, Inc. Endocrine versus Nervous system Released in synapse Close to target cells Signal to release by action potential Short live effect Crisis management Released to bloodstream Can be distant from target cells Different types of signal Long term effect Ongoing processes Neurotransmitters Hormones Both use chemical communication Both are being regulated primarily by negative feedback

6. Copyright © 2010 Pearson Education, Inc. Endocrine System: Overview Acts with the nervous system to coordinate and integrate the activity of body cells Influences metabolic activities by means of hormones transported in the blood Responses occur more slowly but tend to last longer than those of the nervous system Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands

7. Copyright © 2010 Pearson Education, Inc. Endocrine System: Overview Some organs produce both hormones and exocrine products (e.g., pancreas and gonads) The hypothalamus has both neural and endocrine functions Other tissues and organs that produce hormones include adipose cells, thymus, cells in the walls of the small intestine, stomach, kidneys, and heart

8. Copyright © 2010 Pearson Education, Inc. Two main classes 1.Amino acid-based hormones Amino acid derivatives Structurally similar to amino acids Derivative of tyrosine : thyroid hormones catecholamines (Epinephrine, norepinephrin, dopamine), Derivative of tryptophan - melatonine. Hormone structure - based on chemical structure

9. Copyright © 2010 Pearson Education, Inc. Peptide hormones – 2 groups Short polypeptides and small proteins – hormones secreted by heart, thymus, digestive tract, pancreas, hypothalamus (ADH and OT) and anterior pituitary (ACTH, GH, MSH, PRL) Glycoproteins – consist more than 200 amino acids and have carbohydrate side chains. anterior pituitary (TSH, LH and FSH), kidneys (erythropoietin), reproductive organs (inhibin) Hormone structure

10. Copyright © 2010 Pearson Education, Inc. 2.Steroids (Lipid derivatives) Synthesized from cholesterol Gonadal and adrenocortical hormones Hormone structure

11. Copyright © 2010 Pearson Education, Inc. A Structural Classification of Hormones

12. Copyright © 2010 Pearson Education, Inc. Distribution of Hormones in bloodstream Hormones that are released into the blood are being transported in one of 2 ways: Freely circulating Bound to transport protein

13. Copyright © 2010 Pearson Education, Inc. Distribution of Hormones in bloodstream Freely circulating (most hormones) Hormones that are freely circulating remain functional for less than one hour and some as little as 2 minutes Freely circulating hormones are inactivated when: * bind to receptors on target cells * being broken down by cells of the liver or kidneys * being broken down by enzymes in the plasma or interstitial fluid Bound to transport proteins – thyroid and steroid hormones (>1% circulate freely) Remain in circulation longer

14. Copyright © 2010 Pearson Education, Inc. Hormone Concentrations in the Blood Concentrations of circulating hormone reflect: Rate of release Speed of inactivation and removal from the body (clearance rate) Hormones are removed from the blood by: Degrading enzymes The kidneys Liver enzyme systems

15. Copyright © 2010 Pearson Education, Inc. Metabolic clearance rate (MCR) Defines the quantitative removal of hormone from plasma The bulk of hormone is cleared by liver and kidneys Only a small fraction is removed by target tissue protein and amine hormones bind to receptors and are internalized and degraded Steroid and thyroid hormones are degraded after hormone-receptor complex binds to nuclear chromatin 99% of excreted hormone (!) is degraded by enzyme systems

16. Copyright © 2010 Pearson Education, Inc. Mechanisms of Hormone Action Hormone action on target cells 1.Alter plasma membrane permeability of membrane potential by opening or closing ion channels 2.Stimulate synthesis of proteins or regulatory molecules 3.Activate or deactivate enzyme systems 4.Induce secretory activity 5.Stimulate mitosis

17. Copyright © 2010 Pearson Education, Inc. The hormone must interact with a specific receptor in order to affect the target cell In the cell membranes of target cells In the cytoplasm or nucleus Receptors for hormones are located:

18. Copyright © 2010 Pearson Education, Inc. Mechanisms of Hormone Action Two mechanisms, depending on their chemical nature 1.Water-soluble hormones (all amino acid–based hormones except thyroid hormone) Cannot enter the target cells Act on plasma membrane receptors Coupled by G proteins to intracellular second messengers that mediate the target cell’s response 2.Lipid-soluble hormones (steroid and thyroid hormones) Act on intracellular receptors that directly activate genes

19. Copyright © 2010 Pearson Education, Inc. Indirect effect – through G-protein and 2 nd messenger

20. Copyright © 2010 Pearson Education, Inc. Receptors on the cell membrane Hormones do not induces changes in cell activity directly but via the induction of the appearance and action of other agents Hormones are referred to as first messengers and the agents that are activated by the hormones are called second messengers. All amino-acid hormones (with exception of the thyroid hormone) exert their signals through a second messenger system: cAMP PIP

21. Copyright © 2010 Pearson Education, Inc. Receptors on the cell membrane Second messengers function as enzyme activator, inhibitor or cofactor A small number of hormone molecules induce the appearance and activity of many 2 nd messenger molecules – amplification one single hormone can induce the activation of more than one 2 nd messenger Activation of a 2 nd messenger can start a chain of reactions – receptor cascade

22. Copyright © 2010 Pearson Education, Inc. Amino Acid-Based Hormone Action: cAMP Second Messenger Hormone (first messenger) binds to its receptor, which then binds to a G protein The G protein is then activated Activated G protein activates the effector enzyme adenylate cyclase Adenylate cyclase generates cAMP (second messenger) from ATP cAMP activates protein kinases, which then cause cellular effects

23. Copyright © 2010 Pearson Education, Inc. Hormone binds to the receptor and activates G protein G protein binds and activates phospholipase Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both act as second messengers) DAG activates protein kinases; IP 3 triggers release of Ca 2+ stores Ca 2+ (third messenger) alters cellular responses Amino Acid-Based Hormone Action: PIP-Calcium

24. Copyright © 2010 Pearson Education, Inc. Intracellular Receptors and Direct Gene Activation Steroid hormones and thyroid hormone 1.Diffuse into their target cells and bind with intracellular receptors 2.Receptor-hormone complex enters the nucleus 3.Receptor-hormone complex binds to a specific region of DNA 4.This prompts DNA transcription to produce mRNA 5.The mRNA directs protein synthesis

25. Copyright © 2010 Pearson Education, Inc. Location of Receptor Classes of Hormones Principle Mechanism of Action Cell surface receptors (plasma membrane) Proteins and peptides, catecholamines and eicosanoids Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cell Intracellular receptors (cytoplasm and/or nucleus) Steroids and thyroid hormones Alter transcriptional activity of responsive genes http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html

26. Copyright © 2010 Pearson Education, Inc. Target Cell Specificity Hormones circulate to all tissues but only activate cells referred to as target cells Target cells must have specific receptors to which the hormone binds These receptors may be intracellular or located on the plasma membrane

27. Copyright © 2010 Pearson Education, Inc. Interaction of Hormones at Target Cells Three types of hormone interaction Permissiveness – one hormone cannot exert its effects without another hormone being present For example, thyroid hormone increases the number of receptors available for epinephrine at the latter's target cell, thereby increasing epinephrine's effect at that cell. Without the thyroid hormone, epinephrine would only have a weak effect Synergism – more than one hormone produces the same effects on a target cell Antagonism – one or more hormones opposes the action of another hormone

28. Copyright © 2010 Pearson Education, Inc. Target Cell Activation Hormone exert their effects on target cells at very low blood concentrations (ng-10 -9 gr; pg-10 -12 gr) Target cell activation depends on three factors Blood levels of the hormone Relative number of receptors on the target cell The affinity of those receptors for the hormone The time required to effect target cells depends on the hormone - some influence immediately and some (steroids; why?) require hours or days Hormone effect duration also varies and can range between seconds to hours

29. Copyright © 2010 Pearson Education, Inc. down regulation – the presence of the hormone induces a decrease in the receptors concentration; high levels of hormone – cell less sensitive Up regulation – absence of the hormone induces the increase in receptors concentration; Low levels of hormone – cell more sensitive In most systems the maximum biological response is achieved at concentrations of hormone lower than required to occupy all of the receptors on the cell (spare receptors). Examples: insulin stimulates maximum glucose oxidation in adipocytes with only 2-3% of receptors bound LH stimulates maximum testosterone production in Leydig cells when only 1% of receptors are bound Receptors number on target cell

30. Copyright © 2010 Pearson Education, Inc. Control of Hormone Release Blood levels of hormones: Are controlled by negative feedback systems Vary only within a narrow desirable range Hormones are synthesized and released in response to: Humoral stimuli Neural stimuli Hormonal stimuli

31. Copyright © 2010 Pearson Education, Inc. Humoral Stimuli Secretion of hormones in direct response to changing blood levels of ions and nutrients Example: concentration of calcium ions in the blood Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca 2+ concentrations to rise and the stimulus is removed

32. Copyright © 2010 Pearson Education, Inc. Neural Stimuli Neural stimuli – nerve fibers stimulate hormone release Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines Figure 16.5b

33. Copyright © 2010 Pearson Education, Inc. Hormonal Stimuli Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs The hypothalamic hormones stimulate the anterior pituitary In turn, pituitary hormones stimulate targets to secrete still more hormones