Chapter 17 Lecture Outline* Rod R. Seeley Idaho State University Trent D. Stephens Idaho State University Philip Tate Phoenix College *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.

Functional Organization of the Chapter 17 Functional Organization of the Endocrine System

General Characteristics of the Endocrine System 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

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

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.

Examples of Hormone Chemical Structure

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

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

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.

Hormonal Regulation

Positive 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.

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.

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.

Transport and Distribution Hormones dissolve in blood plasma and are transported in unbound or are reversibly bound to plasma proteins. Unbound hormones can diffuse from plasma into interstitial fluid and affect cells As concentration of free hormone molecules increases, more hormone 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.

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

Interaction of Hormones with Their Target Tissues Portion of molecule where hormone binds is called binding site. If the molecule is a receptor (like in a cell membrane) the binding site is called a receptor site hormone/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.

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 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. 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.

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.

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

Intracellular Receptors Receptors: in the cytoplasm or in the nucleus Hormones 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

Activation of G Proteins

Activation of G Proteins 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

G Proteins and Ca2+ Channels

Activation of G Proteins 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

Activation of G Proteins DAG causes production of prostaglandins, which increase smooth muscle contraction IP3 causes increase of Ca2+ in cytoplasm and increases contraction of smooth muscle

Receptors That Directly Alter the Activity of Intracellular Enzymes Cyclic guanine monophosphate (cGMP) produced intracellularly in response to hormone 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

Receptors That Directly Alter the Activity of Intracellular Enzymes 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.

Cascade Effect: Amplification

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.