1. Anatomy and Physiology, Seventh Edition
Rod R. Seeley Idaho State University
Trent D. Stephens Idaho State University
Philip Tate Phoenix College
Chapter 17
Lecture Outline*
*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. Functional Organization of
Chapter 17
Functional Organization of
Endocrine System

3. General Characteristics
Glands that secrete chemical signals (hormones) into circulatory system
Hormone characteristics
Produced in small quantities
Secreted into intercellular space
Transported some distance in circulatory system
Acts on target tissues elsewhere in body
Regulate activities of body structures
Ligands: more general term for chemical signals

4. Regulation of Activities: Comparison of Endocrine and Nervous Systems
Endocrine: amplitude modulated signals.
Amount of hormone determines strength of signal
Onset within minutes of secretion of hormone
Nervous: frequency-modulated signals.
Frequency of action potentials produced by neurons determines strength of signal.
Onset within milliseconds
Two systems actually inseparable
Nervous system secretes neurohormones into circulatory system
Nervous system uses neurotransmitters and neuromodulators as ligands
Some parts of endocrine system innervated directly by nervous system
Regulation of Activities: Comparison of Endocrine and Nervous Systems

5. Intercellular Chemical Signals
Hormones: type of intercellular signal. Produced by cells of endocrine glands, enter circulatory system, and affect distant cells; e.g., estrogen
Autocrine: released by cells and have a local effect on same cell type from which chemical signals released; e.g., prostaglandin
Paracrine: released by cells and affect other cell types locally without being transported in blood; e.g., somatostatin
Pheromones: secreted into environment and modify behavior and physiology; e.g., sex pheromones
Neurohormone: produced by neurons and function like hormones; e.g., oxytocin
Neurotransmitter or neuromodulator: produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells; e.g., acetylcholine.

9. Examples of Hormone Chemical Structure

10. Control of Secretion Rate
Most hormones controlled by negative feedback systems
Most hormones are not secreted at constant rate, but their secretion is regulated by three different methods
The action of a substance other than a hormone on an endocrine gland.
Neural control of endocrine gland.
Control of secretory activity of one endocrine gland by hormone or neurohormone secreted by another endocrine gland

11. Action of Substance Other Than Hormone
An increased blood glucose concentration stimulates increased insulin secretion from the pancreas
Insulin increases glucose uptake by tissues, which decreases blood glucose levels.
Autonomic nervous system also influences insulin secretion

12. Nervous System Regulation
Stimuli such as stress or exercise activate the sympathetic division of the autonomic nervous system
Sympathetic neurons stimulate the release of epinephrine and smaller amounts of norepinephrine from the adrenal medulla. Epinephrine and norepinephrine prepare the body to respond to stressful conditions.
Once the stressful stimuli are removed, less epinephrine is released as a result of decreased stimulation from the autonomic nervous system.

13. Hormonal Regulation

14. Positive and Negative Feedback
During the menstrual cycle, before ovulation, small amounts of estrogen are secreted from the ovary.
Estrogen stimulates the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and luteinizing hormone (LH) from the anterior pituitary
GnRH also stimulates the release of LH from the anterior pituitary
LH causes the release of additional estrogen from the ovary. The GnRH and LH levels in the blood increase because of this positive-feedback effect.

15. Positive and Negative Feedback
During the menstrual cycle, after ovulation, the ovary begins to secrete progesterone in response to LH.
Progesterone inhibits the release of GnRH from the hypothalamus and LH from the anterior pituitary.
Decreased GnRH release from the hypothalamus reduces LH secretion from the anterior pituitary. GnRH and LH levels in the blood decrease because of this negative-feedback effect.

16. Changes in Hormone Secretion Through Time
Chronic hormone regulation. Maintenance of relatively constant concentration of hormone. Thyroid hormone.
Acute hormone regulation. Epinephrine in response to stress.
Cyclic hormone regulation. Female reproductive hormones.

17. Transport and Distribution
Hormones dissolve in blood plasma and are transported in free form or are reversibly bound to plasma proteins
Free form can diffuse from plasma into interstitial fluid and affect cells
As concentration of free hormone molecules increase, more hormones molecules diffuse from capillaries into interstitial spaces to bind to target cells
Lipid soluble hormones diffuse through capillary cells. Water soluble hormones diffuse through pores in capillaries called fenestrae.
A large decrease in plasma protein concentration can result in loss of a hormone from the blood because free hormones are rapidly eliminated from circulation through kidney or liver
Hormones are distributed quickly because they circulate in the blood

18. Metabolism and Excretion
Half-life: The length of time it takes for half a dose of substance to be eliminated from circulatory system
Long half-life: regulate activities that remain at a constant rate through time. Usually lipid soluble and travel in plasma attached to proteins
Short half-life: water-soluble hormones as proteins, epinephrine, norepinephrine. Have a rapid onset and short duration

19. Hormone (Ligand) Interaction with Target Tissues
Portion of molecule where ligand binds is called binding site.
If the molecule is a receptor (like in a cell membrane) the binding site is called a receptor site
Ligand/receptor site is specific; e.g., epinephrine cannot bind to the receptor site for insulin.
The purpose of binding to target tissue is to elicit a response by the target cell.

20. Down-Regulation
Normally, receptor molecules are degraded and replaced on a regular basis.
Down-regulation
Rate at which receptors are synthesized decreases in some cells after the cells are exposed to a ligand.
Combination of ligands 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.
Tissues that exhibit down-regulation are adapted to short-term increases in hormone concentration.
Tissues that respond to hormones maintained at constant levels normally do not exhibit down-regulation.

21. 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. Ovarian cells are now more sensitive to LH, even if the concentration of LH does not change. This causes ovulation.

22. Membrane-Bound Receptors
Receptor: integral proteins with receptor site at extracellular surface. Interact with ligands that cannot pass through the plasma membrane.
Ligands
Water-soluble or large-molecular-weight hormones. Attachment of ligand causes intracellular reaction.
Large proteins, glycoproteins, polypeptides; smaller molecules like epinephrine and norepinephrine

23. Intracellular Receptors
Receptors: in the cytoplasm or in the nucleus
Ligands
Lipid soluble and relatively small molecules; pass through the plasma membrane.
React either with enzymes in the cytoplasm or with DNA to cause transcription and translation
Thyroid hormones, testosterone, estrogen, progesterone, aldosterone, and cortisol

25. Membrane-Bound Receptors
Proteins or glycoproteins that have polypeptide chains folded to cross cell membrane several times
Ligand binds reversibly to receptor site on receptor protein
Three different results of ligand binding
Alteration of membrane permeability. Example: acetylcholine
Activation of G proteins associated with the membrane, causes production of intracellular mediator such as cyclicAMP, leads to activation of intracellular enzymes. Example: LH
Receptors linked to intracellular enzymes through intracellular mediators. Mediators alter activity of intracellular enzymes. Examples: nitric oxide, cyclicGMP, Ca ions.

26. Alteration of Membrane Permeability
Change in permeability of plasma membrane to ions.
Ligand-gated ion channels.
Causes a response in the cell.
Example: neuromuscular junction

28. Activation of G Proteins

30. G Proteins and Intracellular Mediators
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

31. G Proteins and Ca2+ Channels

32. G Proteins and Synthesis of cAMP
Membrane-bound receptors for glucagon are associated with G proteins in liver cells
When glucagon binds to glucagon receptors, the  subunit of the G proteins dissociates from the other subunits and GTP binds to it
The  subunit binds to adenylate cyclase and activates it.
Resulting increase in cAMP activates protein kinase enzymes, which phosphorylate other specific enzymes that break down glycogen and release glucose from the liver cells

33. Activation of G proteins and increase in synthesis of inositol triphosphate (IP3) and diacylglycerol (DAG)
DAG causes production of prostaglandins, which increase smooth muscle contraction
IP3 causes increase of Ca2+ in cytoplasm and increases contraction of smooth muscle

34. Direct Activation of Intracellular Mediators
Cyclic guanine monophosphate (cGMP) produced intracellularly in response to ligand attaching to receptor
cGMP combine with and activate specific enzymes in cytoplasm.
Cell responds
E.g., atrial natriuretic hormone attaches to plasma membrane of kidney cells. cGMP activates enzymes that increase Na+ and water excretion by kidney

35. Membrane-Bound Receptors That Phosphorylate Intracellular Proteins
Ligands 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.

37. Cascade Effect: Amplification

39. Intracellular 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.
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