I. Introduction to endocrine system • A. Classes of Chemical Messengers • 1. Autocrine chemical messengers: released by cells and have a local effect on same cell type from which chemical signals released; e.g., prostaglandin • 2. Paracrine chemical messengers: released by cells and affect other cell types locally without being transported in blood; e.g., somatostatin • 3. Neurotransmitter: produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells; e.g., acetylcholine. • 4. Endocrine chemical messengers: type of intercellular signal. Produced by cells of endocrine glands, enter circulatory system, and affect distant cells; e.g., estrogen
B. Characteristics of the Endocrine System • 1. Glands that secrete chemical messengers (hormones) into circulatory system • 2. Hormone characteristics • Produced in small quantities • Secreted into intercellular space • Transported some distance in circulatory system • Acts on target tissues elsewhere in body • 3. Regulate activities of body structures
C. Comparison of Nervous and Endocrine Systems • Similarities • Both systems associated with the brain • Hypothalamus • Epithalamus • May use same chemical messenger as neurotransmitter and hormone. • Epinephrine • Two systems are cooperative • Nervous system secretes neuroendocrine peptides, or neurohormones, into circulatory system • Some parts of endocrine system innervated directly by nervous system
Differences • Mode of transport • Axon • Blood • Speed of response • Nervous – instant/milliseconds • Endocrine – delayed/seconds • Duration of response • Nervous – milliseconds/seconds • Endocrine – minutes/days • Amplitude vs. frequency
II. General characteristics of hormones A. Stability • 1. Half-life: The length of time it takes for half a dose of substance to be eliminated from circulatory system 2. Long half-life: regulate activities that remain at a constant rate through time. Usually lipid soluble and travel in plasma attached to proteins 3. Short half-life: water-soluble hormones as proteins, epinephrine, norepinephrine. Have a rapid onset and short duration B. Communication • 1. Interaction with target cell • 2. Lipid soluble hormones pass through cell membrane and usually travel to nucleus • 3. Water soluble hormones generally attach to a receptor site on cell membrane C. Distribution • 1. Hormones dissolve in blood plasma and are transported in unbound or are reversibly bound to plasma proteins. • 2. Hormones are distributed quickly because they circulate in the blood.
D. Lipid soluble hormones • 1. must connect to binding proteins in blood or would be catabolized quickly • 2. long half lives as they are protected • 3. tend to have more constant blood levels and regulate basal activity • 3. the liver can attach water soluble radicals to these enzymes so that the kidneys can excrete the hormone • 4. process called conjugation
E. Water soluble hormones • 1. travel freely in circulatory system • 2. larger and don’t diffuse through membranes easily • 3. fenestrated target tissues • 4. short half lives due to proteases circulating in blood • 5. concentrations tend to change rapidly and they regulate activities with rapid onset and short duration
III. Patterns of Hormone Secretion • A. Chronic hormone regulation. 1. Maintenance of relatively constant concentration of hormone. Thyroid hormone. • B. Acute hormone regulation. Epinephrine in response to stress. • C. Episodic (Cyclic) hormone regulation. Female reproductive hormones.
IV. Control of Hormone Secretion • Most hormones controlled by negative feedback systems • In negative feedback, the eventual product turns off the sensor which initiated the products synthesis-self limiting • Common example is the heating of your house • In positive feedback, the product stimulates the sensor to increase its own production-self propagating • Most hormones are not secreted at constant rate, but their secretion is stimulated by three different methods • The action of a substance other than a hormone on an endocrine gland-humoral control-pth and Ca ion • Neural control of endocrine gland-ie adrenal cortex • Control of secretory activity of one endocrine gland by hormone or neurohormone secreted by another endocrine gland-pituitary gland and thyroid
V. Target Tissue Specificity and Response • A. Portion of molecule where hormone binds is called binding site. • B. If the molecule is a receptor (like in a cell membrane) the binding site is called a receptor site • C. hormone/receptor site is specific; e.g., epinephrine cannot bind to the receptor site for insulin. • D. The purpose of binding to target tissue is to elicit a response by the target cell. • E. Diagram shows what happens with larger water soluble hormone which binds to a receptor on the membrane surface
F. Changes in Receptor Number • 1. Normally, receptor molecules are degraded and replaced on a regular basis. • 2. 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. • Explains the desensitization that can occur to some drugs
3. Increase in Receptor Number- 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. • Prepares the ovarian cells’ membranes to prepare for the LH surge that stimulates ovulation
VI. Classes of Receptors A. Lipid soluble hormones • 1. Lipid-soluble hormones bind to nuclear receptors • 2. Lipid soluble hormones are relatively small molecules; pass through the plasma membrane • 3. React either with enzymes in the cytoplasm or with DNA to cause transcription and translation • 4. Examples include thyroid hormones, testosterone, estrogen, progesterone, aldosterone, and cortisol • 5. because of transcription and translation processes, there is a lag time between hormone binding and having its effect exerted
B. Water-soluble hormones • 1. Water-soluble hormones bind to membrane-bound receptors • 2. integral proteins with receptor site at extracellular surface. • 3. Interact with hormones that cannot pass through the plasma membrane. • 4. Attachment of hormone causes intracellular reaction • 5. often binding of hormone causes the production of a second molecule that activates existing internal systems • 6. adrenalin acts this way • 7. faster acting and shorter lived affects when compared to lipid soluble hormones
Action of Nuclear 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.
Membrane-Bound Receptors • 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
Receptors That Phosphorylate Intracellular Proteins • 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.