Biology Exam 2: Nervous vs. Endocrine Systems

Exam 2 Notes Nervous System vs. Endocrine System  The nervous system differs from the endocrine system in several ways (both are  systems of regulation) Nervous system o Nervous system communicates by way of electrical impulses and neurotransmitters. o Nervous system releases neurotransmitters at synapses associated with a specific target cell (such as a neuromuscular junction) o Usually has a local and specific effect (more limited than endocrine) o It reacts quickly to stimulus (usually within 1-10 milliseconds) o Adapts relatively quickly to continuous stimulation  For example, if you put your belt on and it’s tight, every morning after it  doesn’t feel as tight because you have adapted to it. Endocrine system o Communicates by means of hormones (these hormones can be classified by neurotransmitters in the nervous system, however there they are released in synaptic spaces). o Releases chemical substance hormones into bloodstream (via capillary) for general distribution o It can have a general and widespread effect o Reacts more slowly to stimulus (often can take seconds to days) o After stimulation is taken away, it may continue to respond for a long period of time. o Adapts relatively slowly – much longer effect. Endocrine System vs. Exocrine System  Endocrine System o Hormones are released into the blood via capillaries and the endocrine glands are very vascularized and the capillary beds are modified and said to be fenestrated capillaries (larger holes to accommodate larger sizes) o Endocrine can be divided into:    Paracrine – If it is affecting another type of cell Autocrine – If it is affecting itself Exocrine System o The substances made by exocrine glands, such as sweat glands, salivary glands, pancreas, liver (when making bile) all release their substances into a duct. o Recall tubular glands, acinar (alveolar), compound tubular, compound acinar (alveolar)  This is important in treatment, but more important in exocrine glands is how their product is made. o 3 types of exocrine glands:  Apocrine – former belief that the secretion was composed of bits of  apical cytoplasm. Examples include mammary glands. Holocrine – secretion is a mixture of cell fragments and substance of  cell. Examples include oil and sebaceous. Merocrine – cell secretes substance via exocytosis, no part of gland is lost. Examples include salivary, pancreas (when making pancreatic juice), and some kinds of sweat glands. Local vs. Traditional  Local hormones are putting things outside of themselves and are not picked up by capillaries, such as: o Histamines – causes, for example in your nose, if you are allergic to something it sets up a response in your nose only and is local because it doesn’t leave. It creates a local inflammation and is usually useful. o Prostaglandins – reside in smooth muscle cells in uterus – cramps that occur during menstrual cycles are due to release of prostaglandins. o Nitric oxide – not a protein – produced and acts like a hormone; sympathetic  system in the penis and nitric oxide acts as relaxer of blood vessels. Traditional hormones are made by something and picked up by capillaries. The capillaries, in glandular tissue, have bigger holes than other capillaries are fenestrated (have bigger holes). They are then carried throughout the body to their destination via blood. Some are just proteins (insulin) and some are derived by steroids and other things. Hydrophobic vs. Hydrophilic  Hydrophobic means that the substance is not soluble in water. Steroidal-based hormones, such as testosterone, are hydrophobic. This makes a difference on how they are carried throughout their body.   Hydrophilic means that the substance is soluble in water. Insulin is hydrophilic. Hydrophilic will usually be unbound and hydrophobic will usually be bound, but there are exceptions – such as thyroxin (thyroxin hormone) and is not a steroid but comes from an amino acid, tyrosine, and does not like water and is fat soluble. Bound vs. Unbound  If they are soluble in water, they are considered unbound. If they are not soluble in  water, they are considered bound. Bound are usually formed from a cholesterol derivative, but thyroxin is bound and not formed from a cholesterol derivative – it is derived from an amine. If you have a cell that just made insulin, the insulin will enter the capillary and is water-soluble. It can go right on into the plasma of the blood and can just float along with the flow. It has no need to be carried, it is said to be unbound. Unbound are much more vulnerable because they are just swimming along and their half-life is shorter. Recall that if something is bound it will have a greater half-life and is less vulnerable. Chemistry of Compounds    Peptides o Oligopeptides  Small peptides; 3-10 linked amino acids  Examples: angiotension II, ADH, CCK, gonadotropin releasing hormone (GnRH), oxytocin, TSHRH. All of these are tiny and are unbound. o Polypeptides  14-199 linked amino acids  Examples: ACTH, insulin, atrial natriuretic peptide (produced by cardiac muscle cells when the BP is high), gastrin, ghrelin, GH, GHRH, glucagon, calcitonin. Glycoproteins o Have a carbohydrate attached to them o Examples: FSH, LH, TSH o Most have an identical alpha chain of 92 AA’s and variable beta chain o Made in the golgi apparatus Monoamines o Amino acid that retains an amine group o Examples: dopamine, epinephrine, serotonin, melatonin (made by pineal body), thyroxin.  All so far have been water-soluble – except for thyroxin!  Steroidal hormones o Derived from cholesterol – also known as the “short list”:  Progesterone, estrogen, testosterone, cortisol, aldosterone, thyroxin Lecture 13 – September 23, 2011  There are two main methods in which hormones work – cAMP method or gene activating method. cAMP Method  The cAMP method of hormone regulation is sometimes called the second messenger   method. Hormones that work like cAMP are those that are water-soluble. Watersoluble hormones use cAMP, even though some use a variation of cAMP. The hormones on the long list use the cAMP method. Remember not all first messenger hormones act like cAMP. Insulin is not exactly the cAMP method, it is a variation on the theme. If Dr. Alciatore asks to give an example of cAMP on a test, do not give insulin. Shown is a piece of cell membrane:  A feedback mechanism helps maintain a level of homeostasis. Shown is a representation of a feedback mechanism:  You wake up and your fasting glucose reading in the morning is about 90mg/100ml. You have a breakfast of a Snickers and a Dr. Pepper and your glucose level (in extracellular fluid) rises. The following is an example of a “full circle” mechanism: o Digress  Digress from the standard o Sensor  The sensor in this case would be the beta cells of the Islets in the pancreas. o Release insulin  The sensor (beta cells) release insulin. Insulin becomes your first messenger. o Enters blood  Insulin leaves the beta cells and enters the blood via the fenestrated capillaries unbound. Insulin is a traditional hormone. o Looks for target cell  Insulin begins looking for a target cell with a receptor. o Binds to receptor  Insulin (first messenger) binds to a target cell. An example of a target cell would be an adipose cell of the hip.  The union of the first messenger with its receptor causes the G protein to be activated. o GTP  GDP  GTP is converted into GDP – one phosphate is chopped off. This awakens the “sleeping enzyme” adenylate cyclase. Adenylate cyclase is only turned on by the G protein. o ATP  AMP  cAMP  ATP, which came from the mitochondrion of the cell, is converted to AMP – two phosphates are chopped off. AMP is then turned into a cyclic form – cAMP. Adenylate cylcase must be awakened for this to happen. We have now made cAMP – our second messenger. o Second messengers can:  Affect membrane potential, such as opening/closing pores. Synthesize enzymes Turn molecules up or down (pumpers) Encourage secretion Encourage uptake Stimulate mitosis Protein kinases turned on  cAMP runs around turning on protein kinases (unique enzymes for       chemical reactions or activities) unique to the cell – all cells are not  alike. For example, the beta cell has the potential (genetically) to make insulin. If it were an alpha cell, it would make glucagon – so obviously the substances of the cell are different. This is a cascading effect because it causes several things to happen. Destroying of cAMP  Once cAMP has turned on the protein kinases, it must be destroyed. It is typically destroyed by an enzyme called phosphodiesterase. Amount of phosphodiesterase in people may not be normal in some people.  In our alpha cell example, it could stimulate mitosis or encourage uptake of something or opening of a channel. In our beta cell example, it could encourage secretion. Growth hormone is a water-soluble hormone and it may stimulate mitosis. Parathormone (increases calcium, decreases phosphates) will go to an osteoblast and  make it release H+ ions or enzymes to break down collagen fibers – start thinking about what the messengers make their target cell do. If we haven’t eaten all day and our level lowers, the sensor will be the alpha cells in the Islets of the pancreas. Glucagon (the first messenger) will bind to a different receptor, but maybe the same cell. It may encourage the release of glucose or the breakdown of glycogen. Glucose can go into the cell and the cell could use the glucose for energy (maybe right away – muscle cell) or store it as fat. Your level will  go back to normal and is still considered negative feedback. A positive feedback mechanism will keep going and never return to the standard and is sometimes catastrophic. An example of a positive feedback mechanism stopped by a negative feedback mechanism is a blood clot – the blood clot will send more things to clot and clot and clot (positive feedback) and negative feedback comes in so you won’t clot yourself to death and stops the clotting. People who have problems with their estrogen and can’t take the pill because it interferes with the stopping of clotting. Gene Activating Method   The gene activating method of hormone regulation consists of hormones that are not water-soluble (hydrophobic) and mostly steroidal. Gene activating hormones are: progesterone, estrogen, testosterone, cortisol, aldosterone, and thyroxin (thyroid hormone). Recall that thyroxin is not steroid based. The hormones on the short list use the gene activating method. Let’s say a female has low estrogen: o The sensor in this case that will pick up on this level is the hypothalamus – your homeostasis capital. It has sensed that the estrogen level has gone down and wonders what can it do. o The hypothalamus will make FSHRH (long list; cAMP method) o FSHRH will go down to the anterior pituitary and attach to a receptor on its target cell (gonadotroph) and cAMP will happen. o Protein kinases are activated and FSH is made. o FSH will go to an ovary. In the ovary will be an egg and flat cells called follicle cells. FSH is unbound and slips out of the capillary and looks for a receptor on the follicle cell. It will be cAMP method and tell the cell to make estrogen and possibly grow in size (via mitosis). o Estrogen (short list; bound; hydrophobic) will slip out of the cell and go into the blood. o The estrogen will go to an adipose cell in the hip (because the cell membrane is made of fat and estrogen is fat-soluble) and the cell knows estrogen has been made because of the unique nature of the receptor. The receptor can either be in the cytoplasm of the cell or in the nucleus. If it does not find a receptor, it will get right out of there. o Estrogen will now work as a true gene-activating hormone and “crack the genetic whip” and tells the DNA to turn things on and tell it specifically what to do. Usually, it will be telling the mRNA and goes out and commands the making of certain things (such as enzymes for energy storage – such as having enough fat for a sustainable pregnancy). Estrogen loves to affect fat and connective tissue. PIP2 Calcium Signaling Mechanism    Hormones: TRH, ADH, GnRH, Oxytocin, Epinephrine This is considered to be a variation on the cAMP theme. The enzyme phospholipase splits the plasma membrane (phospholipid PIP 2) into DAG (diacylglycerol) and IP3 (inositol triphosphate). DAG Pathway o Hormone binds to its receptor, activating a G protein. o The G protein migrates to a phospholipase molecule and activates it. o Phospholipase removes the phosphate-containing group from the head of the membrane phospholipid, leaving DAG, which remains embedded in the plasma membrane. o DAG activates protein kinases.  IP3 Pathway o The phosphate-containing group removed at step 3 above is IP3. IP3 raises calcium concentration in the cytosol and calcium is released from intracellular storage sites. o This calcium acts like a second (or third) messenger. It is considered a third messenger because the second messenger would be IP3.  If you would have trouble internally with calcium levels, you would not want to use the IP3 pathway. Research is still being done in this area. Control of Hormone  Nervous system – not primary method of control; very gland is affected by the  nervous system, especially the autonomic nervous system. An example includes that blood vessels have muscles in them (arteriole – workhorse vessel) and is penetrated by sympathetic system only and is affected by epinephrine. Medication to block the epinephrine receptor could lower BP. A diuretic is given to lower blood volume. Humoral factors – trying to maintain standard or hormone level; humoral  relationships include the relationship between insulin and glucagon and parathormone and thyrocalcitonin. Hypothalamus/Anterior Pituitary Mechanism Hypothalamus/Anterior Pituitary Mechanism   The hypothalamus has large pairs of nuclei (hunger, thirst, rage) and has a job to effect behavior because of its ability to control the anterior pituitary (once called the “master gland”). The bodies in the neurosecretory make hormones and travel down and are put into a fenestrated primary capillary bed. It then becomes a blood vessel (hypophyseal portal vessel – going from capillary to capillary). When it gets to the tissue of the anterior pituitary, there will be masses of cells called target cells (and function as cAMP):  Somatotrope cells (Acidophil – pink)  Lactotrope cells (Acidophil – pink)  Thyrotropes (Basophil – blue)  Corticotropes (Basophil – blue)  Gonadotropes (Basophil – blue)   It will get out and look for a target cell. Let’s say in the neurosecretory nucleus there is GnRH, the target cell will be called a gonadotrope and finds its receptor here. G protein is activated, enzyme turned on, ATP  cAMP, protein kinases awakened, and ultimately it could tell the cell to make LH. LH (on the long list) will go into the capillary adjacent to it and back into the blood stream unbound and in the male will go to the interstitial cells of Leydig, cAMP happens, and the cell will make testosterone (short list). Testosterone will slip in the cell and could go to a Sertoli (nurse) cell receptor and “cracks the genetic whip and mature sperm. It could go into a capillary and go to skeletal muscle cell to make actin or myosin or go to the male brain and create emotions that lead to aggression (male libido). In order to stop doing something, the hormone inhibin (made by sertoli cell) must tell the hypothalamus to stop releasing the hormone.  Growth Hormone  There is a natural inclination for growth hormone (GH) to be released while you are sleeping at night. Let’s say you have low growth hormone: o Cells make GHRH o GHRH targets somatotrope in anterior pituitary o GH gets into blood with no carrier o Targets cartilage, bone, fat, and muscle cells.   Let’s say GH targets a skeletal muscle cell: o It will find its receptor on the outside and cAMP happens. The message could say to increase in size (make actin and myosin) or increase in number (undergo mitosis). Recall that there is GHRH (growth hormone releasing hormone) and GHIH (growth hormone inhibiting hormone) and both are most likely affecting the same cell. If you have 100 GHRH and only 5 GHIH, the cell will make GH. Hormones, Targets, and Products Hormone Target Product GHRH* Somatotrope GH GHIH (Somatostatin)* Somatotrope Nothing PRH* Lactotrope Prolactin PIH* Lactotrope Nothing TSHRH (TRH) Thyrotrope TSH (targets thyroid follicle) CRH (ACTHRH) Corticotrope ACTH (targets adrenal cortex) FSHRH (GnRH) Gonadotrope LHRH (ICSHRH) Gonadotrope FSH (targets ovary in female and testes in male) LH or ICSH (targets ovary in female and testes in male)