EK B2 Ch3 Endocrine Flashcards
1
Q
endocrine system 1
A
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
2
Q
endocrine v exocrine
A
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
3
Q
endocrine regulation
A
hormone goes into blood, criculates all over body, bind to receptors far away, two other types of regualted autocrine adn paracrine
4
Q
autocrine regulation
A
released by cell turns around and binds to cell, regulating it in some way
5
Q
paracrine regulation
A
- 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!
6
Q
tyrosine derivatives
A
epinephrine, norephinephrine, thyroid hormones
7
Q
hormones binding
A
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
8
Q
peptide hormones
A
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
9
Q
hormones can’t cross membrane…
A
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
10
Q
g protein
A
- gamma, beta and alpha subunits, alpha subunit binds GDP when inactive
11
Q
active adenyl cyclase pathway
A
- 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
12
Q
Adenyl cyclase pathway 1
A
-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
13
Q
phospholipase C pathway 1
A
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!
14
Q
IP3
A
=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
15
Q
PIP2
A
Phosphatidylinositol bisphosphate
16
Q
DAG
A
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
17
Q
3rd signal transduction pathway = receptor tyrosine kinase
A
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
18
Q
NOT LIPID SOLUBLE
A
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
19
Q
Hypothalamus
A
- 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
20
Q
posterior and hypothalamus connection is….
A
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!
21
Q
ADH
A
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
22
Q
oxytocin
A
- responsible for contractions when women go into labor, targeted mammary glands, uterine muscles
- prosocial, military studies
23
Q
anterior pituitary
A
-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
24
Q
TRH
A
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
25
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
26
growth hormone
released by anterior, goes all over body
27
FSH
causes maturation of ovarian follicles in females, sperm production in males
goes to testes or ovaries
28
anterior pituitary hormones
ALL MADE and released by anteiror pituriary
29
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
30
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
31
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
32
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
33
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
34
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
35
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
36
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)
37
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
38
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
39
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!
40
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!
41
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
42
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
43
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
44
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
45
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
46
cortex
outer
47
medulla
inner area
48
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
*
49
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
50
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
51
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
52
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
53
g- protein question
-the alpha subunit holds GTP
54
endocrine system 3
-Endocrine glands produce and secrete hormones
* Endocrine glands have NO ducts
* Hormones secreted directly into blood or interstitial fluid
* Transported by circulatory system to target organs (can be distant)
* Some organs have both endocrine and exocrine secretions (e.g., pancreas)
* Links exist between nervous and endocrine systems
* Nervous system control is faster
* Endocrine system control is slower and longer lasting
* Hallmark of endocrine system is negative feedback control
Criteria using here are how far hormone travels, actually locally or all over the place, endocrine is all over the place
Nervous system electrical signaling very fast, molecules traveling through cirualtory system which tends ot be slower\*
55
exocrine glands 2
-Exocrine glands release secretions into ducts • Sweat, saliva, mucus, milk, digestive juices are exocrine secretions
56
paracrine regulation 2
hormone acts locally on nearby cells
57
Autocrine regulation 2
a hormone acts on the same cells that secreted it
58
Endocrine regulation
hormone is carried by blood and acts on a distant target
59
Classes of hormones
Four classes of hormones:
Steroids: cholesterol-derived (e.g., estrogen, testosterone, progesterone, cortisol)
Tyrosine derivatives (e.g., epinephrine, norepinephrine, thyroid hormones)
Peptides & proteins (everything else)
Fatty acids derivatives (e.g., prostaglandins, leukotrienes)
60
intracellular and extracellular hormones
Hormones bind receptors inside or outside of target cells
Lipid soluble hormones cross the membrane and bind intracellular receptors
Lipid soluble: steroids and thyroid hormone
Peptide/protein hormones can’t cross the membrane and bind extracellular receptors
Non-lipid soluble: everything else
61
Lipid soluble hormones bind intracellular receptors
Steroids and thyroid hormones are lipid-soluble-
1. Steroid hormone plus receptor will directly go into nucelus and change gene expression and act as a transcription factor, goes into intracellular receptors or nucelar receptors b/c its lipid soluble
Lipid soluble hormones cross the cell membrane and enter the nucleus
In the nucleus steroids/thyroid hormone bind to a nuclear hormone receptor
Nuclear hormone receptor is a transcription factor
Hormone binding to nuclear receptor causes a conformational change = ON/OFF
Conformational change may cause the nuclear receptor to (1) move from cytoplasm to nucleus, (2) bind DNA, and (3) turn gene transcription ON/OFF
Change in gene expression mediates hormonal effects
62
peptide hormones bind extracellular receptors
* Peptides and protein hormones cannot cross the cell membrane
Peptide/protein hormones bind a receptor on the plasma membrane
Receptor initiates a signal transduction cascade, information flows to interior of cell
Receptor may initiate signal transduction by two mechanisms:
Receptor has enzymatic activity (e.g., receptor tyrosine kinase)
Receptor is G protein-coupled
End-point for signal transduction is change in gene expression
63
receptors can be enzymes
Some receptors have enzymatic activity in their intracellular domains (e.g., kinase)
Hormone binding switches activity ON/OFF
Example: insulin → binds to insulin receptor kinase → two receptor monomers form a dimer → tyrosine kinase regions on intracellular side become phosphorylated → other proteins bind and become activated → cellular responses
64
g-protein coupled receptors (g proteins 2)
Some hormone receptors act through G-proteins
G-protein forms complex with intracellular portion of receptor
G protein can bind GDP or GTP
Hormone binding → receptor conformational change → receptor activates G-protein
G-protein releases GDP and binds GTP
GDP bound = OFF
GTP bound = ON
Active G-protein then activates other targets
Hormone binding can EITHER switch G-protein ON or OFF
65
cAMP
A common second messenger is cAMP (cyclic AMP)
G-protein turns adenyl cyclase ON at the membrane (ATP → cAMP)
cAMP activates protein kinases
Protein kinases phosphorylate targets, altering their function
Phosphodiesterases hydrolyze cAMP → AMP, turning cAMP pathway OFF
66
Calcium 2+ (2)
Ca2+ also a second messenger
Hormone → hormone receptors → G-protein → Ca2+ ion channel
Ca2+ ion channel opening allows Ca2+ influx to cell
Alternatively, Ca2+ is released from ER
Ca2+ binds calmodulin → conformational change → Ca2+-calmodulin is “ON”
Ca2+-calmodulin complex activates enzymes such as kinases
67
phospholipids
Phospholipids are also second messengers
G protein can activate phospholipase C
Phospholipase C breaks membrane bound PIP2 (phosphotidylinositol 4,5 bisphosphate) into inositol triphosphate (IP3) and diacylglycerol (DAG)
IP3 and DAG act as second messengers
IP3 causes Ca2+ release from ER, activating calmodulin
Activated Ca2+-calmodulin and DAG together activate protein kinase C (PKC)
PKC phosphorylates targets
68
amplification
Hormones can act at low concentrations because of enzymatic amplification
A single receptor binding event → activation of many molecules
1 receptor → G-protein → 100 cAMP → active kinases → 1000s of substrates
69
kinases in endocrine
Kinases transfer P to hydroxyl (-OH) group of: serine, threonine, tyrosine
PHOSPHORYLATION
70
phosphatases
Phosphatases remove P by hydrolysis again work on amino acids with OH
71
HYpothalamus 2
Secretes inhibiting and releasing hormones that control other endocrine glands
Physically connected to pituitary
Produces PROTEIN hormones
GHRH (Growth hormone releasing hormone) promotes GH secretion from pituitary
GHIH (Growth hormone inhibiting hormone) inhibits GH secretion from pituitary
GnRH promotes release of LH and FSH from pituitary
CRF (Corticotropin releasing factor) promotes ACTH secretion from pituitary
TRH (TSH releasing factor) promotes TSH release from pituitary
72
GHRH
(Growth hormone releasing hormone) promotes GH secretion from pituitary
73
GHIH
(Growth hormone inhibiting hormone) inhibits GH secretion from pituitary
74
GnRH
GnRH promotes release of LH and FSH from pituitary
75
CRF (Corticotropin releasing factor)
CRF (Corticotropin releasing factor) promotes ACTH secretion from pituitary
CRF from hypothalamus tells anterior pituitary to release ACTH, stress goes to adrenal cortex\*\* target will be endocrine gland to release next hormone in pathway\*
Adrenocorticotropic hormone (ACTH) is a tropic hormone produced by the anterior pituitary
ACTH binds to receptors on the membrane of the adrenal cortex releasing cortisol, stress shuts down immune system research shows our immune systems are stopping so many precancerous events constantly having these slipups if completely unchecked and bad luck turn into cancer, so by compromising immune system gives tehse abnormalities much more opportunity to turn into something bad
76
TRH (TSH releasing factor)
TRH (TSH releasing factor) promotes TSH release from pituitary
77
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
78
Posterior pituitary
* Posterior pituitary RELEASES oxytocin and ADH
* Hypothalmus PRODUCES oxytocin and ADH
* Oxytocin and ADH travel to posterior pituitary via axons of hypothalamic neurons
* Oxytocin and ADH enter blood only after leaving posterior pituitary
79
ADH/vasopressin
ADH/vasopressin: increases water reabsorption in kidney collecting duct
Increases water reabsorption, blood pressure, decreases urine output
Secreted when plasma osmolarity is high, when blood pressure is low
80
oxytocin 2
Oxytocin: promotes uterine contractions and ejection of milk from milk glands
Involved in mother-child bonding and pro-social behavior
Secreted during suckling, childbirth
81
anterior pituitary 2
Anterior pituitary secretes GH, prolactin, TSH, ACTH, FSH, LH
Secretion controlled by hormones from hypothalamus (see above)
Blood connection between hypothalamus and anterior pituitary (portal system)
82
thyroid gland 2
Secretes TH (TYROSINE DERIVATIVE) and calcitonin (PROTEIN)
TH controls metabolic rate
Basal metabolic rate decreases with age
TH = triiodothyronine (T3, three iodine) and thyroxine (T4, four iodine)
Thyroid hormones are lipid soluble and bind nuclear receptors
TRH → TSH → thyroid secretes TH
TH regulated by negative feedback loop
High TH inhibits TRH and TSH secretion
83
Prolactin
stimulates milk production in milk glands, secretion is stimulated by suckling
prolactin goes to mammory glands, involved in milk secretion
84
TSH
TSH (Thyroid stimulating hormone): causes thyroid hormone secretion, thyroid growth
85
LH
LH: causes ovulation in females, testosterone synthesis in males
86
common pituitary gland defects
Too little GH in childhood
= dwarfism or pituitary dwarf (miniature person)
87
common pituitary gland defects
Too much GH in childhood
gigantism
88
common pituitary gland defects
Too much GH in adulthood
acromegaly (thicker bones in face, head, hands, feet)
89
thyroid gland pathway
TRH → TSH → thyroid secretes TH
TH regulated by negative feedback loop
High TH inhibits TRH and TSH secretion
Calcitonin lowers blood Ca2+
Decreases Ca2+ release from bone and Ca2+ reabsorption in kidney
Feedback regulation by Ca2+
Works oppositely to parathyroid hormone (see below)
90
Thyroid defects
Childhood hypothyroidism can cause cretinism (physical/mental retardation)
Adult hypothyroidism → reduced metabolism, feeling cold, low physical/mental activity
Hyperthyroidism → increased metabolism, feeling hot, weight loss
91
thyroid defects 2
Goiter
Goiter is abnormally large thyroid gland, can reflect TH hypo- or hypersecretion
Hypersecretion of TSH causes thyroid growth
92
Iodine deficiency (thyroid defects)
Iodine deficiency: no T3/T4 synthesis → low TH → increased TSH → thyroid growth
93
parathyroid gland 2
Located next to thyroid gland
Secretes PTH (parathyroid hormone), a PROTEIN
PTH increases Ca2+ levels in blood and interstitial fluid
PTH increases Ca2+ release from bone, reabsorption in kidney, and uptake in intestine
High blood Ca2+ inhibits PTH secretion (negative feedback)
Calcitonin works oppositely to PTH
94
pancreas 2
Pancreas secretes insulin and glucagon, both PROTEINS
Insulin and glucagon are secreted by the islets of Langerhans in the pancreas
Beta cells produce insulin, alpha cells produce glucagon
Insulin decreases blood glucose
Glucagon works oppositely to glucose
Both insulin and glucagon are regulated by negative feedback
After a meal, high blood glucose → insulin secretion
Insulin secretion → glucose uptake from blood → decrease in blood glucose
Fasting → low blood glucose → glucagon secretion → rise in blood glucose
95
insulin 2
Insulin decreases blood glucose
In response to insulin, cells take up glucose from blood
Fat and muscle cells insert GLUT4 transporters into their membranes, which allow glucose to enter passively
Insulin promotes fat storage, protein synthesis
96
glucagon 2
Glucagon works oppositely to glucose
Glucagon raises blood glucose levels
Promotes glycogen → glucose breakdown in liver (glycogenolysis)
Promotes glucose production through gluconeogenesis
Liver cells can release glucose into blood (muscle cells cannot)
97
insulin defects and diabetes
Loss of insulin pathway function can cause diabetes mellitus
Diabetes causes hyperglycemia = high blood glucose (can appear in urine)
Diabetes causes increased metabolism of fats, high blood lipids, atherosclerosis
98
insulin defects and diabetes (hypoglycemia)
Hypoglycemia = low blood glucose
Hypoglycemia may cause loss of consciousness due to lack of brain glucose
Can result from insulin overdose
99
Diabetes causes hyperglycemia =
high blood glucose (can appear in urine)
100
type 1 diabetes
Type 1 diabetes – beta cell loss, causes insulin deficiency
Type 1 is typically childhood onset, can treat with insulin injection
101
type 2 diabetes
Type 2 diabetes – insulin resistance, insulin receptor is unresponsive
Type 2 is typically adult onset
102
aldosterone
* Aldosterone causes Na+ reabsorption and K+ excretion in kidney distal tubule
* Increases water reabsorption, blood pressure, decreases urine output
* Secreted when plasma osmolarity is high, when blood pressure is low
103
Cortisol
* Cortisol increases blood glucose via gluconeogenesis in liver, breakdown of fat
* Cortisol is anti-inflammatory and immunosuppressive
* ADRENAL GLANDS
104
Stress feedback loop 2
Stress promotes CRF (hypothalamus) → ACTH (anterior pituitary) → cortisol
105
Addison’s disease
* Addison’s disease is hypoadrenocorticism = low cortisol
* Many problems, poor glucose regulation, response to stress
* ADRENAL DEFECT 1
106
Cushing’s disease
* Cushing’s disease is hyperadrenocorticism = high cortisol
* Many problems, glucose too high, fat deposited in trunk of body
ADRENAL DEFECT 2
107
Question from QBank
“Bacterial endotoxins may also cause Waterhouse-Friderichsen syndrome, in which acute adrenal failure leads to septic shock. An individual suffering from WF syndrome would NOT be expected to exhibit which symptom?”
Answer= Decreased circulating potassium concentration
## Footnote
WF syndrome is characterized by failure of the adrenal gland following systemic hemorrhage due to infection. As a result of adrenal gland failure, there is no response to ACTH stimulation, and circulating mineralocorticoid and glucocorticoid levels drop precipitously. Deficiency of the glucocorticoids results in hypoglycemia (low blood sugar), and lack of the mineralocorticoids —specifically aldosterone—causes hypotension (low blood pressure and both hyponatremia (low blood Na+ concentrations) and hyperkalemia (elevated blood K+ concentration).
So it is not: low blood sugar, low blood pressure and decreased circulating sodium concentration
Aldosterone’s function is to act on the principal cells of the distal tubule and the collecting duct of the nephron, to upregulate and activate the basolateral Na+/K+ pumps, which pump three sodium ions out of the cell into the interstitial fluid, and two potassium ions into the cell from the interstitial fluid. This creates a concentration gradient which results in reabsorption of Na+ and water into the blood, and the secretion of K+ into the lumen of collecting duct and eventually the urine. If the activity of aldosterone is impaired, each of these symptoms could be seen in a patient suffering from WF syndrome.
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Proteins/fatty acids signal transduction pathway\*
1. Proteins/fatty acids signal transduction pathway\* have to meet extracellular receptor, three scenarios allow message to be conveyed deep into cell: 1. g protein coupled pathway involving cyclic AMP as second messenger. 2. gprotein receptor pathway lots of details second messengers were dag and IP3 and **calcium is always downstream of IP3.** 3. signal transduction pathway\* didn’t involve g protein receptors exactly but receptor tyrosine kinase pathway, just another way for message for hormone carrying to be transduced or conveyed into the cell even when hormone isn’t entering the cell itself
1. Big example for that one is insulin\*
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Tyrosine derivatives
The name tyrosine derivative means body makes these hromones from tyrosine
Tyrosine= **thyroid hormone is lipid soluble and ephinephrine isn’t lipid soluble meets receptor on surface of cell**
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ADH 3
Inc reabsorption of water ADH causes higher blood volume and pressure\*
**if inc volume also inc the pressure\*\*\***
Difference btw gases when inc volume of gas what you mean is inc the volume of container because gas molecules spread out to fill the container, taking same number of molecules, giving them more space so they are under less pressure\* that is the gas law, inc volume means making container bigger, **when talking about blood what we mean by inc volume means more water so more stuff\*\*\* the volume of blood vessels is not changing so putting more fluid into the same size vessel so more pressure inside the vessel**
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If inject too much insulin.....
Injecting too much insulin then going to sleep from hypoglycermia/ from an insulin overdose lose consciousness and they die in their sleep\*
idea that insulin is hard for people to get and so incredibly expensive, how difficult and high stakes it is to get insulin dosing right even when have perfect access to it incredible stressing out there to ration insulin\* for people who cannot afford insulin\* huge healthcare access issue, lots of those cases are people not having enough insulin send people to emergency room on that side its ketoacidosis\*
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FLAT PIG
FLAT PIG= FSH, LH, ACTH, TSH, Prolactin, I= ignore, G growth hormone\*\*\*\*
1. Not break down more bone in perfect world store more calcium in bone harder in older people, bone is a repository of calcium, and if want not reabsorb it as much at kidney, absorption is process in small intestine\* if don’t want it soo much in blood, peeing it out and pooping out let it go
2. FLAT PIG= FSH, LH, ACTH, TSH, Prolactin, I= ignore, G growth hormone\*\*\*\* CRF from hypothalamus tells anterior pituitary to release ACTH, stress goes to adrenal cortex\*\* target will be endocrine gland to release next hormone in pathway\* ACTH binds to receptors on the membrane of the adrenal cortex releasing cortisol, stress shuts down immune system research shows our immune systems are stopping so many precancerous events constantly having these slipups if completely unchecked and bad luck turn into cancer, so by compromising immune system gives tehse abnormalkities much more opportunity to turn into something bad
3. People are really strung out jittery, sweaty lose weight amphetimes, high metabolism taken to a very abnormal extreme is hyperthyroidism\*\*
4. Not break down more bone in perfect world store more calcium in bone harder in older people, bone is a repository of calcium, and if want not reabsorb it as much at kidney, absorption is process in small intestine\* if don’t want it soo much in blood, peeing it out and pooping out let it go
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Growth hormone would promote ......
Growth hormone would promote process cartilage cells in metaphasis of the long bones\*\*\* promotes conversion of cartilage to bone\* in the metapheses of long bones\*
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Both parts of adrenal are....
Both parts of adrenals are involved with stress response, coristol secreted right next to epinephrine
coristol is chronic stress, pathways where those two talk to eachother and boost eachother as well
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The reason if we inc blood volume we inc pressure different than gas laws is because.....
When inc blood volume you can't inc volume of container because its in an artery, whereas gas is like a balloon so therefore increase can increase volume of it and dec pressure
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2. Receptors located at the cell-surface are least likely to bind:
a. glucagon
b. thyroxine
c. insulin
d. epinephrine
b. thyroxine
so will either bind to receptor on surface of cell or inside cell
proteins bind to extracellular sites; so everything else protien peptide binds extrarcelluarly\*
steroids bind intracellularly to their receptors\* aldosteorne, cortiosl, protegerstone, estrogen
**least likely= one that is most liekly to slide into the cell to receptor, thyroxine/thryoid hormone binds to its receptor inside of the cell\* this is a tryosine derviative.**
**Thyroid hormone lipid soluble slides in meets receptor inside cell**
**other one is epin. not lipid soluble and binds to receptors on cell surface\***
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3. iodine deficiency would be LEAST likely to cause:
a. goiter
b. high levels of TSH
c. high levels of T4
d. high levels of TRH
e. slowed metabolism
c. high levels of T4, cannot make t4 then obviously will not have high levels of it\*
iodiine is necessary as part of t3 adn t4 molecule, those numbers actually refer to how many are on the moelcules they are the thyroid hormone being released by thyroid itself and influencing metabolism\*
if do not have enough iodine cannot build a molecule of t3 or t4\*\* VERY VERY VERY IMPORTANT that would be deficient\*\*
if look at chemical structure of T3 and T4 that moelcule has iodine in it! literally cannot have fully made and functional moelcules of T3 adn T4 if you do not have enough iodine its an ingreident in the thyroid hormone\*\*
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6. The posterior pituitary:
a. synthesizes a hormone that increases milk secretion in breast-feeding women.
synthesizes a hormone that acts on the kidney
c. synthesizes a hormone that acts to increase blood volume
d. synthesizes a hormone that promotes uterine contractions during childbirth
e. none of the above
answer is e. none of the above
Reason these are wrong is because of word syntheses!\*\*\*\*\*
poster pituitary doesnt synthesize any of these things\*\* just releases them, for example ADH is created by hypothalamus\* and secreted by posterior pituitary
**Posteiror pitutiary RELEASES ADH and oxytocin**
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Q. 11 Which of the following would likely be true of the patients(s) priors to treatment?
Background- patien A was diagnosed with IDDM (diabiets type I) body is generally unable to produce insulin beacuse of destruction of pancreatic beta cells. Patient B was diagnosed with NIDDM at the age of 50. Her beta cells can produce insulin, but she has been foudn to have insulin resistance.
a. neither patient would have measurable blood insulin levels
b. patient A would exhibit hyperglycemia (high blood sugar) whereas patient B would not
c. Patient B wold exhibit hyperglycemia whereas patient A would not
d. Patient B might have elevated blood insulin levels
e. none of the above
A. is wrong because patient B IS producing insulin would definitely be able to detect insulin, but the cells are not responding to the insulin - so it is wrong to assume neither pt would have measurable blood insulin levels
d. is right because patient B might have even high elevad blood insulin levels, cells aren't responding so may be the case that pancreas pumping out more and more but receptors are not sensitive to it\*\*\* that is the issue with type 2 diabetes\*
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13. the receptor for insulin is:
a. located within the nucleus
b. translated on free ribosomes
c. present at the cell surface
d. made in the nucleolus
e. none of the above
**c. present at the cell surface\*\* FOR INSULIN tyrosine kinase receptor**
TRANSMEMBRANE RECEPTOR
so made and then inserted into plasma membrane so that is bound ribosomes on ER\*\*
so b is wrong, translated on ribosomes in ER. it is not located within the nucleus, and it is not made in the nucleolus
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16. Intracellular receptors are least likely to bind:
a. estrogen
b. testosterone
c. thyroxine
d. growth hormone
the answer is d= growth hormone
**Growth hormone is a protein, so will defintely bind to a receptor on the cell's surface\***
thryoxine- inside\*\* special tyrosine derivative\*
estrogen and testosterone are steroids
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19. Which of the following is a second messenger?
a. Diacylglycerol
b. Protein Kinase A
c. Protein Kinase C
d. Calmodulin
answer is a
downstream of second messengers, not called second messengers
can be part of the same pathways but they are not, come after second messenger stage\*
**second messengers are: cAMP, IP3, Calcium, or Diacycylgylcerol (aka DAG)**
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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
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drawing of phosphodiesterase breaking the phosphodiester bond
phosphodiesterase breaks a phosphodiester bond\*\*\*\* product is 5' AMP
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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
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What does 5' AMP look like?
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Which of the following is also a second messenger?
a. ATP
b. Protein Phosphatase
c. Inositol 1,4,5-triphosphate
d. Adenylate cylcase
**c. Inositol 1,4,5-triphosphate**
wrong-d. obviously enzyme with that last phrase "ase" enzyme that forms, proteins/enzymes are not second messengers!
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22. cAMP is hydrolyzed to form:
a. ATO
b. 5' ADP
c. adenylate cyclase
d. 5'AMP
d. 5'AMP
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7. Higher than normal calcium levels would most liekly casue:
a. release of calcitonin by the parathyroid
b. decreased uptake of calcium along the GI tract
c. increased release of calcium from intracellular stores
d. increased reabsorption of calcium in the kidneys
e. release of parathyroid hormone
7. answer is b=
b. decreased uptake of calcium along the GI tract
If already have a lot of calcium in blood, you want a mechanism that would reduce calcium in blood bring it back down! conservation of calcium in blood is a homeostatic variable liek glucose cannot let it go too high or too low, if too high abnormally high, first of all secrete calcitonin but then looking further downstream in terms of what calcitonin would do is cause you to absorb less calcium from food\* to bring down amount of calcium in blood and make it not go higher\* why B is correct!!!
d- wrong becuase means calcium in filtrate leaving body gotten rid of would instead be reabsorption in kidneys and go back into blood, so reABSORBED means on the way out you get more in the kidney, already have too much calcium in the blood you do not want to reabsorb calcium from the filtrate---want to pee out how much is going into filtratre/ pee it out and get rid of it through excretion\*\*
notice this is not resoprtion/breaking done bone, this is REABSORPTION\*\* taking place in kidney\* Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
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Is calmodulin a second messenger?
NO
Calmodulin is a protein that just hangs out in cytoplasm and it doesn't really do very much unless Ca is there\* just a protein and sometimes as part of the system Ca will act with calmodulin if calcium spikes can cause things to happen just by itself, sometimes hte calcium has to work together with calmodulin but calmodulin by itself is just sitting there\* **it is not by itself created a second messenger\*** sometimes referred to as calcium binding protein\*
