03/28/16 Ch. 10 Endocrine System Endocrine System General Principles The Endocrine System: Principles of Chemical Communication and Functions of the Endocrine System Classes of Chemical Messengers (table 10.1) Autocrine o Chemical released by specialized cell, chemical will feed back and influence the activity of the cell Paracrine o Chemical released by special cells, chemical is then going to diffuse nearby and effect cells in the same general location o Bloodstream not involved o Histamine when damaged tissue releases histamine, it’s going to affect immune cells nearby Neurotransmitter o Ex. Is acetylcholine in the muscular o Chemical released by neuron, diffuse across synaptic cleft, and affect the post-synaptic cell Endocrine o Chemicals released by specialized cells often in glands, will be picked up by the cardiovascular system/blood vessels, and then carried throughout the body. Then going to affect target tissues at different sites. o Hormone—a chemical that’s released in one place, travels through blood, and affects cells at a distant site Hormones are made in glands Not all tissues in the body respond to hormones. b/c the response requires a receptor. If there’s no receptor, the tissue doesn’t respond Anywhere the cardiovascular system goes, you’ll have the hormone General Functions of the Endocrine System 1. Metabolism 2. Control of food intake and digestion 3. Tissue development 4. Ion concentration in the blood 5. Water balance (one of the most life-threatening deviations from homeostasis) 6. Heart rate and blood pressure 7. Blood glucose 8. Reproduction 9. Urine contractions and milk release 10. Immune system Characteristics of the Endocrine System Endocrine glands o o o o Not to be confused with exocrine glands—ducted glands like sweat glands, there are a lot in the digestive system Endocrine glands release substances into the bloodstream; they don’t have ducts Release hormones Target tissue—hormone receptors Hormones affect target tissues What makes something a target? That’s the presence of receptors for the hormones. If the receptors don’t work, your body can’t respond to the hormones. trouble When a hormone interacts with its receptor, it induces a change in the receptor, and this changes the physiology in the cell (induce physiological changes) The things that are regulated by hormones tend to be things that are important for every cell in your body. Hormones are great for regulating a general effect. Metabolism increasing or decreasing Thyroid hormones regulate entire body at once—Advantage in coordinating all body cells, but useless when we think about neurotransmitters in muscle contractions—hormones are NOT involved with this Endocrine System Hormones The Endocrine System: Hormones Hormones Hormones—a chemical secreted by specialized cells that travels through the blood to distance target sites. o What makes something a target of a hormone is whether or not it has a receptor for that hormone o Since it’s in the bloodstream, it moves throughout the body. What it affects in the body depends on how easy it can get in and out of the bloodstream Chemical Nature of Hormones Lipid-soluble hormones Water-soluble hormones Lipid-Soluble Hormones Plasma membrane keeps things in and out of cell o Water can’t pass through membrane, so is separate Anything that’s lipid-soluble will dissolve and go right through the membrane Nonpolar Include steroid hormones, thyroid hormones, and fatty acid derivatives When these get into the bloodstream and get everywhere in the body, how do they go out of the blood? –They go through the walls of the cells that line the blood vessels. Essentially, these hormones are going to get everywhere in your body. What’s the base of blood? --Blood is basically water/an aqueous solution. Fat and water separate, so there’s trouble in getting them into the blood, so… …The body transports lipid-soluble hormones (small) attached to binding proteins (large). This helps the hormones dissolve in blood really well, but it prevents them from doing their job of finding and binding to a receptor, so if you want to use the hormone, you have to separate it from the protein so it can function/do its thing. Water-Soluble Hormones Polar o Dissolve right in blood o Include protein hormones, peptide hormones, and amino acid derivatives o Circulate as free hormones Don’t require a binding protein b/c they dissolve very well in water But it needs to get out of the blood and into the tissue, so it can interact with receptors on the cell and have an effect. Since it’s not lipid-soluble, it can’t pass through the membranes. It needs help: can use transport mechanisms or if there’s a leak space between cells, then the proteins can diffuse out between cells. Fenestrated capillaries have windows btw cells that hormones can just go through Degradation of Hormones Released hormones don’t stick around forever; they become metabolized All hormones are destroyed in the circulation in the blood or at the target Half-life—affected by many factors o Half-life—measure of how long the hormone sticks around If you inject 10 units of hormones, the half-life tells you how long it takes for you to get down to 5 units, and then 2.5 o Affected by many factors Lot of variation among hormones Some hormones have a half-life of seconds Others of das General guidelines: A hormone attached to a binding protein isn’t gonna get degraded quickly. Free lipid-soluble hormones tend to be longer lasting than water soluble proteins (where their proteins get eaten up by proteases very quickly) o Thyroid regulates metabolism and has a long half-life. Slow to implement, but last a long time o But with regulating blood pressure—we don’t want that to linger; the physiological changes are going to happen very rapidly, and it’d be better to use a protein with a short half-life for this. Endocrine System Regulation of Hormone Secretion Stimulation of Hormone Release Humoral stimuli o “Humoral” refers to fluid o Trigger cells in a gland to release hormone Neural stimuli o Adrenal gland When sympathetic nervous system is activated, it’ll send signals to adrenal and increase cortisol secretion—part of the stress access. That stress is psychological/neural in nature Hormonal stimuli o Hormones influence the secretion of other hormones Hypothalamus and pituitary o Can also inhibit the release Sympathetic and parasympathetic nervous systems have opposite effects Pituitary gland Pituitary gland called the “master gland” o Body can’t function normally without pituitary o Pituitary releases hormones. Those hormones are going to cause other glands to release their hormones. Ultimately, the activity of the pituitary gland is under the control of the hypothalamus. o The (neurons in the) hypothalamus releases special stimulating hormones called “releasing hormones”. These releasing hormones stimulate cells in the anterior pituitary to release their hormones. These hormones are going to be in the general circulation/go everywhere in the body. They’re then gonna interact with the receptors on gland cells. Those cells are gonna be excited and release other hormones. Those hormones are then going to circulate throughout the body and affect a broad variety of target cells. o Anything that’s a releasing hormone is released by the hypothalamus and acts on pituitary gland o Releasing hormones travel through the blood stream to the anterior pituitary. They do not get in the general circulation. Once these releasing hormones stimulate the cell in the anterior pituitary, they’re gonna increase their release of hormones that are gonna travel throughout the body and affect specific endocrine/target cells. Those target cells will release the hormone into the blood where it’ll produce a general response. Ex. HPA access—Hypothalamic Pituitary Adrenal access When you feel stressed, cells will stimulate a neuron in the hypothalamus to release CRF—Corticotrophin Releasing Factor/CRH—Corticotrophin Releasing Hormone. This gets picked up by the blood vessels and carried to the anterior pituitary. In the anterior pituitary, CRH is going to bind to receptors in the cells and will make a hormone called ACTH. ACTH will then travel to the blood and get carried to the adrenal gland. ACTH then act with the receptors and cells in the adrenal gland—it’ll stimulate them to release cortisol. Cortisol will get carried throughout your blood and affect many different tissues (i.e. brain, fat, muscles) General idea: Stimulation of pituitary will release another hormone that’ll travel throughout the body and act on endocrine cells. Those are going to release another hormone that are gonna have general effects on target cells. Negative Feedback Don’t want to keep stimulating cortisol; there must be a mechanism to shut it off o In this case, the hormone released by the endocrine organ will exert negative feedback to slow the hormones that stimulate its relase o Cortisol is gonna go everywhere, but it’s also gonna come back to the pituitary and hypothalamus where it’ll inhibit the release of CRH and ACTH Decrease the release of CRH and ACTH less stimulation, so the cortisol levels are gonna decrease The hormone ultimately reduces its own release Positive Feedback Very rare Something is going to stimulate its own release More and more and more hormone until something “blows up” o Can trick your body into a positive feedback loop, but if no intervention, then those are always lethal Positive feedback in the reproductive axis is normal o Leutinizng hormone triggers ovulation. Hypothalamus stimulates the release of the stimulating hormone, that trophic hormone will act at the endocrine cell. That endocrine cell will release a hormone that will affect target cell. Now, the hormone released by the endocrine cell is going to also go back to the hypothalamus and pituitary and instead of shutting things down, it’s going to stimulate them so that there’s a massive release of that hormone. Levels will increase repeatedly. Again, positive feedback loop is very rare. Around time of ovulation, there’s a change. A switch goes, so the estrogen that exerted negative feedback will now exert positive feedback. Endocrine System The Pituitary The Endocrine System: The Pituitary Gland and its Hormones Pituitary gland illustrates all the principles of the endocrine system and puts them together nicely Pituitary Gland The master gland o Very important for normal regulation and normal physiology Controlled by hypothalamus Divided into the anterior pituitary and posterior pituitary o Anterior pituitary (adenohypophysis) Has a connection to the hypothalamus through blood vessels (not a direct connection) o Posterior pituitary (neurohypophysis) An extension of neurons that reside in the hypothalamus o Functionally and structurally, they are very differently Hypothalamus-Pituitary Sella turcica—pocket that houses the pituitary; provides a pouch for the pituitary gland so it doesn’t get squished by the rest of the brain Hypothalamus connects to pituitary gland through the infundibulum Pituitary Gland Anterior and posterior pituitary are kinda mushed together o Anterior connected to hypothalamus through blood vessels o Posterior gonna have axons from neurons that live up in the hypothalamus. So the cell bodies will be up in the hypothalamus. They’ll send their axon bodies down the infundibulum into the posterior pituitary. So when the cell bodies in the hypothalamus get excited, they send action potentials down their axons. And instead of neurotransmitters, we’re gonna release hormones. The axons are neurons—why it’s called the neurohypophysis Diagram: Direct connection of posterior pituitary through the infundibulum Posterior pituitary will release 2 hormones: o 1. ADH (vasopressin) o 2. Oxytocin All other hormones released from anterior pituitary Blood vessels connect anterior pituitary and hypothalamus, but it’s not a direct connection. B/c the axons don’t make it down o Releasing hormones are picked up by capillaries. The capillaries are gonna carry that hormone into the anterior pituitary. When it’s in the anterior pituitary, it’s gonna be released. And that’s what’s gonna exert its effect o This blood vessel is called the HPP—Hypophalamic Pituitary Portal Vasculature o Normally, substances are picked up by capillaries, they go through circulation, through the heart, and then through another capillary bed. Then they induce the release of other hormones i.e. Lungs in digestion Bottom line: Capillaries heart capillaries o However, there are some places in the body where we go from capillary bed to capillary bed w/o passing through the heart; called a portal system. Hypophalamic Pituitary Portal System o Pituitary hormones that are released from the anterior pituitary: Have a general idea of what these do (10.2): Growth hormone Gland ACTH TSH FSH LH MSH Prolactin Hormone Target Tissue Response Growth hormone Most tissues Increases gene expression, breakdown Pituitary gland Anterior of lipids, and release of fatty acids from cells; increases blood glucose levels Thyroid-stimulating hormone (TSH) Thyroid gland Increases thyroid hormone secretion (thyroxine and triiodothyronine) Adrenocorticotropic hormone (ACTH) Adrenal cortex Increases secretion of glucocorticoid hormones, such as cortisol; increases skin pigmentation at high concentrations Melanocyte-stimulating hormone (MSH) Melanocytes in skin Increases melanin production in melanocytes to make skin darker in color Luteinizing hormone (LH) or Ovary in females, interstitial cell–stimulating testis in males Promotes ovulation and progesterone hormone (ICSH) testosterone synthesis and support for sperm cell production in testis production in ovary; promotes Follicle-stimulating hormone Follicles in ovary in Promotes follicle maturation and (FSH) females, estrogen secretion in ovary; promotes sperm cell production in testis seminiferous tubules in males Prolactin Ovary and Stimulates milk production and mammary gland in prolongs progesterone secretion females, testis in males Posterior Antidiuretic hormone (ADH) Kidney following ovulation and during pregnancy in women; increases sensitivity to LH in males Conserves water; constricts blood vessels Oxytocin Uterus Increases uterine contractions Mammary gland Increases milk letdown from mammary glands Anterior pituitary (diagram): How does it work? o Stimuli from the nervous system. When these are excited, there’s an increase in the amount of releasing hormone. If these are inhibited, there’ll be a decrease. Either way, a hormone’s gonna get released into the blood vessels. Hormone(s) will get carried down the HPP system, down into the anterior pituitary. Here, those hormones that stimulate and inhibit the release of other hormones are gonna come out of circulation and affect cells in the anterior pituitary. o So, releasing factors and inhibiting factors are gonna affect the pituitary. Those cells are gonna release different hormones back into the circulation and back into the capillaries, where they’ll be carried out into other tissues. In many cases, these target tissues will be other glands i.e. adrenal gland, gonads Posterior pituitary Much simpler o We’re gonna activate or inhibit neurons. If they’re activated, we’ll get a release; action potentials coming down at the terminals of those cells, we’ll get the release of hormone that’ll go right into the blood and out into the body where it’ll affect target tissues. The Endocrine System: Mechanisms of Hormone Action Lipid-soluble (thyroid or steroid) and water-soluble (glucagon, prolactin) hormones diagram: Each type probably exerts an effect using a different mechanism Lipid-soluble hormones dissolve their way right through the membrane; get into the cell easily. These hormones have the opportunity to act with receptors inside the cells itself. o Typically, they end up interacting with a receptor in the nucleus. When this happens, the receptor will bind to DNA, alter gene expression, change the proteins present in the cell and that’ll have profound effects on how the cell works. Water-soluble hormones can’t pass through the membrane o So if there’s a nuclear receptor for a water-soluble hormone, the hormone will have to be actively transported o For most water-soluble hormones, the receptor is on the membrane. When the hormone binds to it, it’ll start a biochemical cascade that’ll eventually lead to specific cellular responses. G-protein (for membrane bound receptors) --a complex of proteins. When it’s active, it’s gonna alter the activity of other enzymes. So when my hormone binds to my membrane receptor, it’ll change the shape of this G-protein complex. And will expose active sites. Those are gonna lead to a change in another enzyme that’s gonna increase the synthesis of molecule that’ll interact with other proteins and change their activities, and so on and so forth G-proteins start this biochemical cascade that’s eventually gonna change the function of proteins in the cell and consequently change the way the cell is functioning Diagram: Lipid-soluble hormone diffuses through plasma membrane. A couple things can happen: o 1. Some hormones have cytoplasmic receptors that they’ll bind to, and then get carried to the nucleus. o 2. Other hormones have their receptors already in the nucleus Bottom line, there’s a receptor bound to its hormone. That’s gonna then interact with DNA. Which is gonna alter transcription (process of converting DNA sequence into mRNA. mRNA will then move to cytoplasm where it’ll interact with ribosomes. Ribosomes will make proteins. Those newly synthesized proteins will alter the function of the cell. Lipid-soluble hormones are slower than water solubles Hormones have a relatively short half-life, but the effect of the hormones lasts long. Lipid-soluble hormones have a long lag btw when the hormone’s released and when you see the effect, but those effects are gonna last for a long period of time End: Know what G-protein is and how it works Hormone binds to receptor, that changes activity of G protein, and there’ll be a cascade of events that leads to a cellular response.