Chp. 17 FUNCTIONAL ORG. Char.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 17-1 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 17-2 1
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. 17-3 Examples of Hormone Chemical Structure 17-4 2
1. 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 17-5 2. 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. 17-6 3
3. Hormonal Regulation 17-7 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 LH causes the release of additional estrogen from the ovary. The GnRH and LH levels in the blood increase because of this positivefeedback effect. 17-8 4
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. 17-9 Changes in Hormone Secretion Through Time a) Chronic hormone regulation. Maintenance of relatively constant concentration of hormone. Thyroid hormone. b) Acute hormone regulation. Epinephrine in response to stress. c) Cyclic hormone regulation. Female reproductive hormones. 17-10 5
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. 17-11 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 17-12 6
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. 17-13 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 largemolecular-weight hormones--causes intracellular reaction. Large proteins, glycoproteins, polypeptides; smaller molecules like epinephrine and norepinephrine 17-14 7
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 17-15 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 17-16 8
Activation of G Proteins (like a cascade) Membrane-bound receptors for glucagon are associated with G proteins in liver cells When glucagon binds to glucagon receptors, the a subunit of the G proteins dissociates from the other subunits and GTP binds to it The a 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 17-17 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 17-18 9
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. 17-19 Cascade Effect: Amplification 17-20 10
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 receptorhormone complex Estrogen and testosterone produce different proteins in cells that cause the differing secondary sexual characteristics of females and males. 17-21 17-22 11