1. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Chapter 16 The Endocrine System Part A

2. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Objectives:  Categorize hormones according to their mode of action  match and select from a given list with 100% accuracy  Describe control of hormone secretion  List the major endocrine glands & identify their location and secretion  List the disease conditions related to hypo and hyper- secretion of each kind of hormone  Be able to discuss the role of hormones in homeostasis  Match and select from a given list with 100% accuracy  Be able to answer critical thinking questions

3. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Endocrine System: Overview  Endocrine system:  The body’s second great controlling system  Influences metabolic activities of cells  Functions through hormones  Endocrine glands:  Ductless glands  Have rich vascular and lymphatic drainage  Release their products into surrounding tissue fluid  Their products are called hormones  Hormones are long-distance chemical signals  They are carried by blood or lymph to various body cells

4. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Endocrine System: Overview  Endocrine glands include:  Pituitary  Thyroid  Parathyroid  Adrenal  Pineal  Thymus  Pancreas: Produce both hormones and exocrine products  Gonads: Produce both hormones and exocrine products

5. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Endocrine System: Overview  The hypothalamus:  Is a neuroendocrine organ  Has both: Neural and endocrine functions  Other tissues and organs that produce hormones:  Adipose cells  Pockets of cells in the walls of:  Small intestine  Stomach  Kidneys  Heart PLAY

6. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Major Endocrine Organs Figure 16.1

7. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Autocrines and Paracrines  Autocrines:  Are local chemical messengers  Exert their effect on the same cells that secrete them  Paracrines  Locally acting chemicals  They affect cells other than those that secrete them  Autocrines & paracrines are not hormones (Why?)

8. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hormones  Hormones:  Cellular substances secreted into the extracellular fluids  Regulate the metabolic function of other cells  Have lag times ranging from seconds to hours  Tend to have prolonged effects  Are classified as:  Amino acid-based hormones (most hormones)  Steroids (gonadal & adrenocortical)  Eicosanoids:  Biologically active lipids with local hormone–like activity

9. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hormone Action  Hormones alter target cell activity by one of two mechanisms:  Plasma membrane receptor binding:  Works thru 2 nd messengers and regulatory G proteins  For water soluble amino acid–based hormones (except thyroxine)  Intracellular receptor binding:  Direct gene activation  For lipid soluble steroid hormones & thyroxine  The precise response depends on the type of the target cell

10. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Hormone Action  Hormones produce one or more of the following cellular changes in target cells  Alter plasma membrane permeability or action potential, or both  Stimulate protein or regulatory molecules synthesis  Activate or deactivate enzymes  Induce secretory activity  Stimulate mitosis PLAY

11. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Action of Amino Acid-Based Hormones:  Cyclic AMP (cAMP; 2 nd Messenger) signaling mechanism:  Three plasma membrane components interact to determine intracellular cAMP level:  A hormone receptor  A signal transducer (G protein)  An effector enzyme (Adenylate cyclase)

12. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Action of Amino Acid-Based Hormones: cont’d  The hormone (1 st messenger) binds to its receptor  Receptor then binds to G protein  G protein is activated by binding GTP (GDP is displaced)  G protein activates adenylate cyclase (effector enzyme)  Adenylate cyclase generates cAMP (second messenger) from ATP  cAMP activates protein kinases  Kinases then cause cellular effects

13. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Receptor Hormone A Receptor GTP ATP cAMP Inactive protein kinase A Active protein kinase A Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channels, etc.) Adenylate cyclaseHormone B GDP Extracellular fluid Cytoplasm GsGs GiGi 1 2 3 4 32 1 5 Figure 16.2 Amino Acid-Based Hormone Action: cAMP Second Messenger

14. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Hormone (first messenger) binds to its receptor  Receptor then binds to G q protein  G q protein is activated by binding GTP (GDP displaced)  G q protein binds and activates phospholipase C  Phospholipase C splits phospholipid PIP 2 ( phosphatidyl Inositol Bisphosphate) into:  Diacylglycerol (DAG) and  IP 3 ( Inositol Triphosphate) Both DAG & IP 3 act as second messengers Amino Acid-Based Hormone Action: PIP 2 -Calcium

15. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  DAG activates protein kinases C 1  IP 3 triggers release of Ca 2+ stores (from ER & others)  Released Ca 2+ :  Acts as a 3 rd messenger, and  Alters cellular responses:  Directly by:  Altering the activity of specific enzymes & membrane Ca 2+ channels  Indirectly by:  Binding calmodulin (intracellular regulatory protein) activating enzymes that amplify cellular response Amino Acid-Based Hormone Action: PIP-Calcium

16. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings GTP PIP 2 IP 3 Receptor GTP Catecholamines TRH ADH GnRH Oxytocin Triggers responses of target cell GDP Extracellular fluid Cytoplasm Inactive protein kinase C Active protein kinase C Phospholipase C GqGq Ca 2+ Ca 2+ - calmodulin Hormone Endoplasmic reticulum DAG 1 2 3 4 5 5 6 Figure 16.3 Amino Acid-Based Hormone Action: PIP Mechanism

17. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Steroid Hormones  Steroid (& thyroid) hormones diffuse into target cells  They bind and activate intracellular receptors (forming a complex)  Complex go to nuclear chromatin  The hormone receptor binds specifically to the DNA  Binding prompts transcription (mRNA synthesis)  The mRNA is translated into a specific protein molecules  The protein brings about a cellular effect  In the absence of the hormone, receptors are tied into:  Receptor-chaperonin complex (exception is thyroid receptors)

18. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Steroid hormone Steroid hormone Cytoplasm Receptor- chaperonin complex Molecular chaperones Receptor-hormone complex Hormone response elements Binding Transcription Chromatin mRNA Nucleus New protein Translation Ribosome mRNA Figure 16.4

19. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Break Slisde Biol2401.33248 Mon, 22.’13

20. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Target Cell Specificity  Hormones circulate (in blood &lymph) to all tissues  But only activate cells referred to as target cells  Target cells must have hormone-specific receptors  These receptors may be located:  Inside the cell (intracellular)  On the plasma membrane

21. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Target Cell Specificity  Examples of hormone activity  ACTH receptors:  Only found on certain cells of the adrenal cortex  Thyroxin receptors:  Found on nearly all cells of the body

22. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Target Cell Activation  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  Up-regulation:  Hormone stimulates target cells form more receptors  Down-regulation:  Target cells lose receptors in response to the hormone

23. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hormone Concentrations in the Blood  Hormones circulate in the blood in two forms:  Free form  Bound form  Steroids and thyroid hormone:  Are bound to plasma proteins  All others are free

24. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hormone Concentrations in the Blood  Concentrations of circulating hormone reflect:  Rate of release  Speed of inactivation & removal from the body  Hormones are removed from the blood by:  Degrading enzymes  The kidneys  Liver enzyme systems

25. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Interaction of Hormones at Target Cells  Three types of hormone interaction  Permissiveness:  One hormone exerts its effects only when another hormone is present  Ex. Thyroid hormone & reproductive system development  Synergism:  More than one hormone produces the same effects on a target cell  Ex. Glucagon and epinephrine in releasing liver glucose  Antagonism:  One hormones opposes the action of another hormone  Ex. Insulin & glucagon on blood glucose

26. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Control of Hormone Release  Blood levels of hormones:  Are controlled by negative feedback systems  Vary only within a narrow desirable range  Hormones are synthesized & released in response to:  Humoral stimuli  Neural stimuli  Hormonal stimuli

27. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Humoral Stimuli  Humoral stimuli  Secretion in response to blood level change of:  Ions and nutrients  Example:  Concentration of blood calcium ions  Declining blood Ca 2+ level stimulates:  Secretion of parathyroid hormone (PTH) by the parathyroid glands  PTH causes Ca 2+ concentrations to rise and the stimulus is removed

28. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Humoral Stimuli Figure 16.5a

29. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Neural Stimuli  Neural stimuli:  Nerve fibers stimulate hormone release  Preganglionic sympathetic fibers stimulate the adrenal medulla to secrete catecholamines Figure 16.5b

30. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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

31. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hormonal Stimuli Figure 16.5c

32. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Nervous System Modulation  The nervous system modifies:  The stimulation of endocrine glands  Endocrine gland negative feedback mechanisms  The nervous system can override normal endocrine controls  For example, control of blood glucose levels:  Normally the endocrine system maintains blood glucose  Under stress, the body needs more glucose  The hypothalamus and the sympathetic nervous system are activated to supply ample glucose

33. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Biol2401. Break Slide