EK B2 Ch3 Endocrine Flashcards
endocrine system 1
glands that produce and secrete hormones, not by way of ducts, they secrete hormones directly into blood! means hormones get moved around by circualtory system adn can effect very distant targets, hormone once gets into blood can bind to something far away -often works with nervous system but nervous system obviously works much faster -endocrine control usually slower but long lasting
endocrine v exocrine
exocrine release secretions into ducts so like pancreas has an exocrine function it releases all of its digestive enzymes through ducts, travel through duct system to get to ducts -other similar things/terms endocrine
endocrine regulation
hormone goes into blood, criculates all over body, bind to receptors far away, two other types of regualted autocrine adn paracrine
autocrine regulation
released by cell turns around and binds to cell, regulating it in some way
paracrine regulation
- secreted locally, doesn’t secrete all over the body just binds to nearby cells
- so also a lot of growth factors taht work this way and they are considered paracrine regualtors, in cluster of cells one cell will release a growth factor and make one cell in region grow more!
tyrosine derivatives
epinephrine, norephinephrine, thyroid hormones
hormones binding
can bind inside or outside cell depending if hormone is lipid soluble, if lipid soluble hromone can go through membrane and bind to receptor inside the cell! then cell and receptor usually go ot nuc and act as transcription factor and alter DNA expression
peptide hormones
can’t cross cell membrane, so binds to g protien coupled receptor or other receptor on cell surface, and then send the message deeper into the cell using signal transduction pathway*
- bind extracellular receptors like g protein coupled receptor, called that because coupled to a g protein that then activates a second messenger like cAMP or one of the other ones
hormones can’t cross membrane…
need to meet receptor on extracellular surface on membrane - so first way this can happen is through adenyl cyclase pathway, inactive g protein receptor with nothing bound to it, and then next to that have G protein holding a GDP molecule so that is a sign that the G protein is not active! b/c it is bound to gdp, so can see nearby enzyme adenylul cyclase but whole pathway is off right now and enzyme is just sitting there
g protein
- gamma, beta and alpha subunits, alpha subunit binds GDP when inactive
active adenyl cyclase pathway
- when active hormone swipes out GDP with GTP, sign that this protein is on and G protein is active
- then what protein does is activate adenyl cyclase, which is enzyme that converts ATP to cyclic AMP first example of second messenger, structure of cAMP in notes, this is very much like atp except only one phosphate group and weirdly looping around on itself which makes cyclic amp cyclic phospahte group doing some stunt looping around to 3’ O, that is what makes it cyclic, cyclic amp in turn activates protein kinase A
- protein kinase A as a kinase is responsible for phosphorlating other enzymes in the cell, so when we talk about this mention activation cascades, one thing phosphoraltes another molecule which phosphorlates another moelcule etc all which originates with hormone binding to cell, like game of telephone inside cell, also as part of that get amplification of signal, one protein kinase A can activate 10 other enzymes which can also activate 10 other enzymes, benefit of having signal transduction cascade, a lot of bang for your buck small number of hormones binding to receptors can get a pretty loud message inside of the cell
Adenyl cyclase pathway 1
-turned off cAMP deactivated by enzyme called phosphodiesterase, cleave ring part of cyclic AMP and turn it back into regular amp -other thing happens to turn off this pathway, GTP being held by G protein gets hydrolyzed to GDP** so G proteins have this built in GTPase activity and once we are back to GDP we consider the G protein not active anymore
phospholipase C pathway 1
another ex of where there is a receptor binds a hormone that activates a G protein, here it is shown in active form with GTP bound
-enzyme nearby is phospholipase C- which cleaves PIP2 into IP3 and DAG, PIP2 in membrane and DAG remains in membrane
IP3 floats off into cytoplasm, dag and ip3 are both considered second messengers!
IP3
=inositol triphosphate
-second messenger, binds to ER membrane and opens up Calcium channels, Ca2+ does signaling alone or with Calmodulin
-calcium concentrations kept very low in cytoplasm of cells, when open up calcium channel in membrane of ER, calcium will passively flow out of ER and into cytoplasm, other ex of when open Ca2+ channel in membrane, and ca2+ will come rushing into cell because in cytoplasm concentrations are really low
-here allows Ca2+ to rush out of ER and also considered a second messenger, involved in further downstream signaling and sometimes it partners with protein called Calmodulin, a calcium binding protein, and two of them hand and hand run around and activate some things, other things calcium ions activate by themselves but a lot of different downstream options depending on what kind of cell we are in
PIP2
Phosphatidylinositol bisphosphate
DAG
diacylglycerol -activates protein kinase C together with Calcium, so basically if in a cAMP system protein kinase A is the big work horse, and if in phospholipase C pathway then its doing heavy lifting of running around and phosphorylating enzymes
3rd signal transduction pathway = receptor tyrosine kinase
receptor itself acts as enzyme, a kinase! - so on extracellular side looking at structure, this is an example involving insulin, receptor is a dimer, two parts and then on the bottom intracellular side whole bunch of tyr side chains coming off of receptor, when hormone binds for ex when insulin binds to receptor, going down to bottom picture, hormone binds to each subunit, receptor dimerizes meaning two parts come together, and then tyrosines on intracellular side pick up phosphate groups from ATP, and then phosphate groups transferred to other enzymes ex of receptor on intracellular side acting as kinase, picks up phosphates from ATP then moves them onto other enzymes so phosphorylating other stuff
tyrosine kinase- two subunits, intraecellular side whole bunch of tyrosine part of proteins structure important but right now just sticking out into cytoplasm, in lower picture active hormone insulin will bind to each subunit and then the receptor will dimerize and two subunits will come together and form a dimer, triggering tyrosine on intracellular side to pick up phosphate groups* getting phosphate groups from atp* and then other enzymes can be phosphorylated in other words they can come by and pick up phosphate group, that phosphate group can be transferred to other enzymes** so the whole receptor especially the intresellar side can be considered a kinase becuase phsophorlated*
whatever needs to be phoisphorlated comes over because it is stuck in the membrane= whole names receptor tyrosine kinase
NOT LIPID SOLUBLE
probably proteins, if is lipid soluble slides through membrane and meets receptors inside cell, ex steroid like cholesterol glide through membrane easily, plenty of peptides or proteins that need to do this to meet receptors on surface of cell, tyrosine derivatives split difference -epinephrine is an ex of tyrosine derivative that uses an extracellular receptor, thyroid hormone ex of tyrosine derivative that is lipid soluble and able to use an INTRACELLULAR receptor! only two things in category that split difference in terms of whether lipid soluble or not and if they combine with receptors
Hypothalamus
- referred to as master gland, same with pituitary gland, two competing masters -everything it produces is a protein! 2 roles: 1. interaction with posterior pitutiary and other 2. with anterior pituitary - in brain hypothalamus is above pitutiary gland, which dangles down has two parts posterior pituitary and anterior pitutiary, each one interacts with hypothamlus but each does it in slightly different ways
posterior and hypothalamus connection is….
neuron connection
hypothalamus sends signal to posterior pitutiary
hormones ADH and oxytocin are made in hypothalamus travel down these axons and released from posterior pitutiary into blood stream
posteior pituitary doesn’t make any of its own hormones it release ADH and oxytocin made in hypothalamus! remember hypothalamus doesn’t release oxytocin! sythensies it but posterior pituitary releases it!
ADH
targets kidney collecting duct, antidieretic hormone, makes you pee less, dieretic would make you pee more does opposite
-if retain water blood volume goes up and blood pressure goes up because of increased water! so ADH has bottom line effect or raising blood pressure
oxytocin
- responsible for contractions when women go into labor, targeted mammary glands, uterine muscles
- prosocial, military studies
anterior pituitary
-connection btw hypothalamus and other part of pituitary, blood connection not neuronal, portal vessels NOT NEURONS, neurons are yellow portal blood vessels shown in pink, hypothalamus talking to anterior pituitary and then anterior sends out a ton of different hormones, FSH, TSH, Prolactin, MSH (ignore), GH and targets else where in the body
TRH
hypothalamus has a hormone called TRH, goes to anterior pit. and tlels anterior to send out TSH which stands for thyroid stimulating hormone, then TSH relay race goes to thyroid gland and then causes thyroid gland to release thyroid hormone
ACTH
another pathway where there is something from hypothalamus tells ant. pitutiary to release ACTH -releases coritsol, stress pathway -prolactan, releases milk
(Adrenocorticotropic hormone) causes secretion of cortisol from adrenal cortex ACTH secretion is triggered by stress
growth hormone
released by anterior, goes all over body
FSH
causes maturation of ovarian follicles in females, sperm production in males
goes to testes or ovaries
anterior pituitary hormones
ALL MADE and released by anteiror pituriary
GHRH
- hypothalamus releases GHRH promotes GH secretion and is released by anteiror pituitary
- actual signaling molecule or hormone goes through hypothalamus to anterior pitutiary and then the anterior produces and releases another hormone in response, so that interaction is different than what we saw with hypothalamus and posterior pitutiary which has a connection of neuron stretching down to posteiror pituitary
- hypothalamus sends these signals to anterior pituitary, where it is made and then released
common pituitary gland defects ex. too little GH in childhood
- do not grow to full stature, traditionally called dwarf
too much GH people can grow too much/ gigantism
too much GH in adulthood: as a result of tumor, anterior pituiary tumors causes anterior pitutiary to start massively pumping out some hormone, if start over producing growth hormone as result, don’t get taller but get acromegaly where bones, face, head and hands start really thickening, like lincoln ppl though he had that
thyroid
2 roles: one mediated by TH and other calcitonin, protein, focusing on thyroid hormone -it controls our baseline metabolic rate, people say TH or thyroid hromone when biologists when crazy with naming, but it encompasses T3 or T4, two different variations on moelcule -T3, T4 or TH or trioxy are the same thing, T3 has 3 iodines on it, and T4 has 4 iodines on it, doesnt make a different in terms of function -thyroid hormone tyrosine derivative lipid soluble, binds to receptor inside the cell, but together with repcetor acts as transcription factor inside nucleus to bind to DNA, impact on metabolism
negative feedback thyroid
- T3/T4 does negative feedback on anterior pituitary and hypothalamus, look page 90
- high levels of Thyroid hormone puts breaks on hypothalamus, less TRH and less TSH because breaks on anterior pituiary, so means thyroid simulated less so should bring down the levels of t3 and t4, idea of negative feedback able to keep the concentration of something within a narrow range
thyroid defects childhood hypothyroidism
-kid born with low levels of hypothyroidism, historically one of the major causes of mental retardation, now testing thyroid hromone cocnentraiton in babies is routine very easy to give someone thyroid hromoen supplements if miss it tragic to miss it and compromsie someone’s brain development, HUGE DEAL hypothyroidsim= hypo means too little thryoid hromone, hyper means too much, those prefixes will aply to hypergylcemia or hypoglycemia
adult hypothyroidism
low baseline metabolic rate, cold, sluggish, depresed, ppl present with depression considered good practie to test thyroid hormone concentration because can actually cause depression
hyperthyroidism
very hot, lose weight, people are really strung out, jittery, anxious, like on amphetimnes, effects of metabolism cranked up too high
high metabolism taken to a very abnormal extreme is hyperthyroidism
Graves Disease
autoimmune disease in which antibody activates TSH receptor so remember TSH is released by the anterior pituiary and it binds to a receptor located on the thyroid, TSH thryoid stimulating hormone is suppose to stimulate thryoid to release, but if have antibody binding to that receptor would over stimulate thyroid becuase no negatvie feedback control and antibody telling feedback to go go go one way to get hyperthryodism, not brought down by usual feedback loops
remember it- think graves disease, grave site has all those tomb stones think antibody on tsh rceptor on the thyroid (tomb stone on tsh receptor blocking)
Goiter
-when thyroid is massively overstimulated and produces too much, called goiter big growth in neck -can happen with hypothyroidism or hyperthyroidism, very dramatic mass develops from an enlarged thyroid, do not see it much in US -another cause of goiter is iodine deficiency, can think about feedback loop, iodine part of molecule of thyroid hormone, variants that contained 3 or 4 iodines, if have an iodine deficiency meaning cannot literally make thyroid hormone to complete molecule another cause of hypothyroidism which causes adults to feel sluggish or depressed but can also potentially cause goiter in following way= if you are not able to make thyroid hormone, if cannot make T3 or T4, if no thyroid hormone, anterior pituitary secretes more trh and tsh means these hormones are shouting at thyroid to produce and produce but thyroid cannot because no iodine which can also result in thyroid becoming overgrown and causing goiter
thyroid also involved in regulating blood concentrations of calcium
-calcitonin=lowers blood Ca2+ -body wants to keep concentration of ca in blood in narrow range, Calcitonin TONES DOWN Ca in blood, if goes too high thyroid releases calcitonin, which has a net result to reduce blood calcium concentration -causes less Ca2+ to be released from bone and keep more in bone, have less calcium reabsorption in the kidney, meaning let body pee out more Ca to get rid of it -third way is absorb less Ca from food, just not take it in first place from food, targeting digestive tract
parathyroid gland
-right besides thryoid, few little glands secrete parathyrid hormone another protein that does the exact opposite of what Calcitonin does -if Ca dips too low, pth is secerted by parathrypid galnd and do a few things that raise Ca concentration in the blood! which to break down bone to release ca, to cause more calcium to be reabsorbed in kidney, and more to be taken up through food through walls of small intestine!
pancreas
-talked a bunch for digestive system, now in endocrine chapter focus on endocrine part of pancreas, secretes 2 hormones insulin and glucagon, both proteins, they are secreted from an area of the pancreas called islets of Langerhans, beta cells produce insulin and alpha cells produce glucagon, important because there are so many passages on diabetes, beta cells cells that produce insulin!
insulin and glucagon
-released in respone to changes in blood glucose concentration, action of insulin is to decrease blood glucose, secrete insulin in fed state, after just eaten and do all the digestion processes and asborption, blood sugar is high because all nutrients have been absorbed in blood, when pancreas will release insulin! -turns of how insulin decreases blood glucose, allows cells to take up glucose from blood, and specifically causes blood to insert glut4 transporterr into membranes -insulin has these muscle and fat cells, transporters in memrbane allow glucose to come passively into cell, glucose will come in if door is there, and insulin causes door to be put into the wall
insulin 2
most famous for allowing glcose to be taken up by cells, also true because insulin working at a moment where body well fed, nutrients high, promotes fat storage and protein syntehsis, acts in that context when there is a lot of available nutrients that has to be dealt with
glucagon
-glucagon works oppositely to insulin, meaning it raises blood glucose levels, where insulin would lower blood glucose levels! -if raise blood glucose levels that could involve breakdown of glycogen in liver, could involve gluconeogenesis in liver probably biggest ways we have to raise blood glucose concentrations -both insulin and glucagon respond directly to blood level of glucose, negative feedback situation under normal situations blood can keep glucose concentrations in tight range, if too high release insulin if too low release glucagon, so able to regulate blood glucose concentrations tightly
diabetes
type I- body doesnt produce insulin otherwise no way of bringing down blood sugar after they eat type II- usually occurs in adults where ppl do produce insulin but receptors like on muscle cells receptors not sensitive enough so blood sugar remains too high -usually because body not using glucose effectively, ppl with diabetes will metabolize fats more, do more beta oxidation get more ketone bodies, because mobilziing fats soo much get fatty deposits in arteires, get clogging of arteries from cholesterol, most common cause of death from diabetes is cardiovascular incidents like heart attacks
adrenal glands
sit on top of kidneys, kidneys on small of your back, right there on top are adrenal glands, two parts an inner area called adrenal medulla, and outer area called adrenal cortex
Adrenal cortex is outside, adrenal medulla is inside
cortex
outer
medulla
inner area
adrenal medulla 2
- secretes epinephrine and norepinephrine
- BOTH are tyrosine derivatives bind to extracellular receptors! -do a fight or flight response -neuro endocrine gland, works v closely with sympathetic nervous system that does fight or flight response
*
adrenal cortex
secretes 2 hormones, both are steroids 1. aldoesterone= acts on kidney, inc water reabsorption, water going back to blood and therefore raises blood pressure! 2. cortisol= part of a class of hormones called glucocorticoids, cortisol is the most famous ones, all inc blood sugar and cause greater break down of fats, mobilizing resources
adrenal defects
Addison’s disease= too little cortisol causes problems to poor glucose regulation, abnormal response to stress Cushing’s disease= condition with too much cortiosl, fat deposited because is too high
Cushing’s disease founded by babe paley’s father
Stress pathway
Hypothalamus- releases CRF goes to Anterior Pituitary- releases ACTH goes to adrenal gland, specifically adrenal cortex, which releases glucoroticoids, incl. cortisol, WHICH RAISES BLOOD GLUCOSE*** so if have high CRF high ACTH high glucocorticoid, amped up signal all the way down through pathway
Higher than normal blood calcium levels would most likely cause:
- calcintonin is released by thyroid not parathyroid! =decreased uptake of calcium along the GI tract, if blood calcium is too high, want blood calcium concentration to be within a tight narrow range, if blood calcium is too high, release calcitonin, causes more uptake of calcium by bone, do anything it can to get calcium out of blood, more uptake of calcium by the bone, less absorption of calcium from food, if blood calcium is already too high calcitonin reacts by causing less calcium to be absorbed from dietary sources along the digestive tract! 3. third way has to do with kidney, in terms of reabsorption of calcium, if blood levels of calcium are already too high calcintonin will act to cause less to be reabsorbed, peeing out less calcium in that case
Pituitary gland 2
Pituitary is a “master gland”
Produces PROTEIN hormones
Posterior pituitary RELEASES oxytocin and ADH
Anterior pituitary secretes GH, prolactin, TSH, ACTH, FSH, LH
adenyl cyclase pathway summary 3
hormone first messenger and binds to receptor, activating g protein
gprotein now in active form, know that because holding GTP
activated GTP protein in turn activates adendyl cyclase- which converts ATP to cyclic AMP***
cyclic part where basically phosphate group is forming this really really weird looking ring, very strange molecule and cyclic amp activates protein kinase A and other things happen in cell but eventually this enzyme phosphodiesterase will turn off cAMP***
phosphodiesterase breaks a phosphodiester bond**** product is 5’ AMP
drawing of phosphodiesterase breaking the phosphodiester bond
phosphodiesterase breaks a phosphodiester bond**** product is 5’ AMP
Phospholipase C pathway Review
Dag stays in membrane
IP3 moves into cell BOTH ARE SECOND MESSENGERS
IP3 first move is to remove calcium from endoplasmic reticulum, example of a ligate gated calcium channel
calcium then moves into cytoplasm, sometimes does signally alone sometimes it teams up with calmodulin hanging around
calcium also considered a second messenger
calcium can also go and activate DAG and then Ca and Dag together will be activated and in turn activate protein kinase C
What does 5’ AMP look like?
