Final Flashcards
1
Q
Hormones
A
- are synthesized as prohormones or preprohormones
- > biologically inactive, need to remove pre/pro to become active (enzyme)
- can have effects locally or systemically (diff routes)
- > endocrine, paracrine, autocrine and intracrine
- in order for a hormone to exert an effect must bind to a receptor
- can be dimerized, heterodimers, homodimers, homotrimer, heterotrimer
- receptors are on the cell membrane, nuclear membrane, inside nucleus, or inside the cytoplasm
2
Q
Endocrine Organs
A
- Hypothalamus
- Pineal Gland
- Anterior or Posterior Pituitary Glands
- Thyroid gland
- Parathyroid Gland
- Adrenal Glands
- Kidneys
- Pancreas
- Ovaries or Testes
3
Q
Hormone 1/2 Life
A
- hormone metabolism
- how long does it take for 50% of a hormone to be utilized by the body (animal efficiency)
- metabolic clearance rate (MCR)
- the half life of a hormone is how fast it moves through the plasma and is broken down
- determines how bioactive the hormone is in the body
- the longer the half life and MCR, means it has a longer bioactive length
4
Q
Hormones Produced in the hypothalamus
A
- GHRH (growth hormone releasing hormone)
- CRH (corticotropin releasing hormone)
- TRH (thyrotropin releasing hormone)
- GnRH (gonadotropin releasing hormone)
- GHIH (growth hormone inhibiting hormone)
- Dopamine
- Oxytocin
- rel in anterior pituitary - ADH (Antidiuretic hormone), arginine vasopressin (AVP) or Vasopressin
- rel in anterior pituitary
5
Q
Hormones PRODUCED AND RELEASED from Anterior Pituitary Gland
A
- GH (growth hormone)
- PRL (prolactin)
- TSH (thyroid stimulating hormone)
- FSH (follicle stimulating hormone)
- LH (Luteinizing Hormone)
- ACTH (adrenocorticotropic hormone)
6
Q
Thyroid Gland Hormones
A
- make thyroid hormone from the thyroid gland
- intermediates:
1. T3 (triiodothyronine)
2. T4 (thyroxine)
3. Calcitonin (regulate calcium levels in blood stream)
7
Q
Parathyroid Gland Hormones
A
- PTH (parathyroid hormone)
8
Q
Adrenal Gland Hormones
A
- cortisol
- aldosterone
- adrenal androgens
- epinephrine
- norepinephrine
9
Q
Pancreas Hormones
A
- Insulin
2. Glucagon
10
Q
Ovaries Hormones
A
- E2 (Estrogen)
2. P4 (Progesterone)
11
Q
Testes Hormones
A
- Testosterone
12
Q
Hypophyseal Portal System
A
- hypothalamus needs major blood supply to support feedback mechanisms (neg feedback regulatory system)
- > connects what happens at the level of the hypothalamus to the pituitary gland
- major blood supply in the endocrine system
- region between hypothalamus and pituitary gland is the infundibular stalk
- structure diffusely located within the hypothalamus is the median eminence
- hypophyseal portal vein (from hypothalamus to anterior pituitary gland)
- inferior hypophyseal arteries (under pit glands) and superior hypophyseal artery (goes into infundibular stalk)
- hypothalamic artery (goes into hypothalamus)
- nerves go from hypothalamus into Post Pit Gland
- > regulatory hormones go into the median eminence and then an activation will be released in the anterior pituitary
- nuclei that go to posterior pituitary are SON AND PVN
13
Q
Anterior Pituitary Gland
A
- also called pars distalis, adenohypophysis, anterior lobe
- produces AND releases hormones
- oxytocin and ADH are prod in the hypothalamus, but released in the anterior pituitary
- larger than the posterior pituitary
- originates from Rathke’s Pouch
- the anterior pituitary gland is derived from tissue in the roof of the mouth
- Rathke’s pouch is epithelial tissue that began pinching off and eventually was alone
- It then migrated to the brain and attached to form the anterior P.G
- 4 to 5 weeks of human gestation ant pit becomes visible
- functionally mature at 20 weeks gestation
- roof of mouth depression creates an intermediate lobe and then regresses
- intermediate lobe can be called pars intermedia
- > will continue to function in monkeys, rodents and dogs
- intermediate lobe produces hormone POMC (proopiomelanocortin)
- > is cleaved into two substances: alpha-MSH and a little ACTH
- > in humans since regressed gives function to anterior pituitary
- glandular bc hormones are produced and released here
- under influence of hormones in the median eminence
- pulsatile and sicklet function
14
Q
Posterior Pituitary Gland
A
- also called pars nervosa, neurohypophysis, posterior lobe
- only releases hormones, not glandular
- neural origin, from ventral hypothalamus where it was derived from
- 3 neurons in the hypothalamus with nerve ends in post pit
- the neurohypophysis (post pit gland) consists of axons and nerve endings with their cell bodies residing in the hypothalamus
- magnocellular neurons nerve ends go here
15
Q
Nuclei vs Ganglia
A
- Nuclei
- a collection of cell bodies inside the CNS - Ganglia
- a collection of cell bodies outside the CNS
16
Q
Nuclei in the hypothalamus
A
- PVN = paraventricular nuclei
- contains magnocellular and parvocellular cell bodies
- releases TRH(thyrotropin RH) and CRH(corticotropin RH) - SON = supraoptic nuclei
- only contains magnocellular cell bodies
- releases ADH and oxytocin
- nuclei contain A LOT of NERVE/NEURON CELL BODIES
- IF SAYS parvocellular or magnocellular NEURONS, it does not go into these structures, on its own in hypothalamus
- IF SAYS parvocellular cell goes inside the structures
17
Q
Magnocellular Neurons
A
- originate in the hypothalamus and end in posterior pituitary
18
Q
Parvocellular Neurons
A
- originate in hypothalamus and end in median eminence
19
Q
Oxytocin in Females/Males
A
- G-alpha-q receptor
- second activation of phospholipase C (PLC)
- release calcium eventually
- produced by hypothalamus, released in AP
- in female targets the UTERUS and MAMMARY GLANDS
- when activated contractions begin and oxytocin signals up-regulate the receptors until birth (POS FEEDBACK)
- plays a role in milk letdown, works with prolactin during breast stimulation
- during lactation there are receptors in the breast and levels of oxytocin increase
- to induce labor give oxytocin (hard to produce milk if there is a lack as well)
- binds in males at the level of the leydig cells in the testicles (cuddle hormone)
20
Q
ADH, AVP, or Vasopressin
A
- produced by hypothalamus
- targets the KIDNEY
- increases water reabsorption at the level of the kidney, water uptake
- volume of urine decreases because takes up water
- Alcohol is an inhibitor of ADH
- > prevents water uptake and electrolytes
- > Urine output increases due to this
21
Q
Nuclei in the hypothalamus
A
- SON- supraoptic nuclei
- contains magnocellular cell bodies (posterior pit)
- releases oxytocin and ADH - PVN-paraventricular nuclei
- contains magnocellular and parvocellular cell bodies (median eminence and post pit)
- release TRH (thyrotropin RH) and CRH (corticotropin RH) - *ARN- arcuate nuclei
- linked to appetite center (contribute to homeostasis)
- parvocellular cell bodies (median eminence)
- release GnRH, GHRH, Dopamine and GHIH - AVPV- anteroventral periventricular nuclei
- release GHIH
- parvocellular cell bodies (median eminence) - *VMH- Ventromedial hypothalamus nuclei
- satiety center (contribute to homeostasis)
- parvocellular cell bodies (median eminence)
- releases GHIH and GHRH - *SCN-suprachiasmatic nuclei
- circadian rhythms (24 hour body cycle)
- a center (contribute to homeostasis)
22
Q
Thryroptroph
A
- Thyrotropin RH prod from the PVN (med em) in hypo targets thyrotroph cell in AP
- releases Thyroid Stim Hormone (TSH) targets the thyroid and releases 3 (triiodothyronine), T4 (thyroxine), Calcitonin (regulate calcium levels in blood stream)
- ends with negative feedback
23
Q
Gonadotroph
A
- GnRH from ARN target gonadotroph cells in AP (G alpha q)
- produce FSH and LH
- target testicles(G alpha s) to produce testosterone, negative feedback
OR - target the ovaries(G alpha s) to produce estrogen and progesterone
24
Q
Corticotroph
A
- Corticotropin RH (CRH) from PVN targets the corticotroph in the AP (G alpha s)
- produces POMC which releases ACTH and alpha-MSH endorphine
- ACTH (adrenocorticotropic hormone) goes through blood stream and binds to G alpha s on adrenal gland
- releases androgens and cortisol
25
Q
Somatotroph
A
- 50% of pop of cells in ant pit
- GHRH (galpha s) and GHIH (Galphai) binds to somatotroph and releases GH
- growth hormone targets the bone, skeletal muscle and liver
26
Q
Lactotroph
A
- Dopamine is released in the median eminence and targets lactotroph (Galphai) produces prolactin
- prolactin travels via blood stream targets the mammary gland and binds to a heterodimer
- milk letdown production occurs
27
Q
POMC
A
- precursor for ACTH
- released from Corticotropin RH (CRH)- Galpha s receptor
- creates beta endorphines and alpha-MSH
- produces ACTH when indiv is under stress
- ACTH released in pulses, but increases at 4 am when sleeping (why handle stress better earlier in morning, by noon all stress hormones gone)
- CRH to POMC to ACTH to adrenal gland
- ACTH binds to adrenal gland (G alpa s) and produces cortisol and androgens
28
Q
MSH
A
- overproduction is linked to skin cancer
- humans prod small amount
- receptors for FSH are found here
29
Q
Beta endorphines
A
- naturally occurring opioid
- psychoactive chemical (narcotic)
- endogenous
30
Q
Dopamine
A
- produced in the hypothalamus
- released into the median eminence (ARN)
- targets lactotroph cells and bind to G alpha i receptor
- inhibits the release of prolactin
- reward motivated behavior/learning when in CNS
- can act in the PNS as a chemical messenger
- precursor is L-DOPA (derived in brain by conv LDOPA to dopamine)
- > enzyme that converts is DOPA-decarboxylase
- when dopamine is HIGH, prolactin is LOW
- absence of dopamine, increases oxytocin, ADH, and TRH
- suckling stimulates inhibition of dopamine, inc in prolactin
31
Q
Parkinsons
A
- linked to L-DOPA, have neurons that secrete very low L-DOPA levels (neurons dont work)
- can give L-DOPA and Dopamine to treat
32
Q
Prolactin
A
- LOW when dopamine is HIGH
- linked in females for nesting
- prolactin targets the mammary gland and binds to a heterodimer receptor
- causes intracellular event (Jak Stat Pathway)
- get proliferation, development, maturation of mammary gland (milk protein synthesis and let down)
- suckling stimulates increase
33
Q
CNS vs Endocrine
A
- compliment to each other
- work together to maintain homeostasis
- positive and negative feedback systems
1. Endocrine - slow responses
- delayed responses
- indirect bc travels along the blood stream
- use chemicals/proteins to get response (neurotransmitters)
- longer effect
- neurotransmitters bind with high affinity
- can have endocrine, paracrine, autocrine, intracrine signaling mechanisms
2. CNS (brain and SC) - very quick responses
- immediate response
- direct because travel along neurons
- short effect
- neurotransmitters release massive amounts
- neurotransmitters bind with low affinity
- use chemicals to get response (neurotransmitters)
34
Q
KD
A
- refers to receptors and dissociation of hormone from the receptor (measure of affinity)
- it is the equilibrium dissociation constant
- the concentration of hormone at which 50% of available receptors are bound to a hormone
- inversely proportional with affinity
- lower KD = higher the affinity of the receptor for the hormone
35
Q
G-Protein Linked Receptor Structure
A
- a class of proteins
- a 7 transmembrane receptor associated with 3 subunits that are heterotrimeric g-proteins (alpha, beta, gamma)
- receptor crosses the membrane 7 times and has a N and C terminal end
- the N terminal is on the outside of the cell and the C terminal is intracellular
- 3 subunits= alpha, beta and gamma
- hormone binds extracellularly, can not diffuse across the membrane, based on the KD will eventually dissociate
- if the hormone is an agonist it will trigger a rxn inside the cell
- if the hormone is an antagonist it will suppress a rxn inside with a receptor
36
Q
G-Protein linked receptor
- GDP/GTP and subunit functions
A
- GDP becomes GTP inside the cell
- GTP exerts an affect on the alpha subunit, causing it to break off and beta/gamma become a heterodimer
- beta and gamma then create a downstream affect
- downstream effect is based on varying alpha subunit
37
Q
Gprotein linked receptor
- alpha subunit function and types
A
- acts as an activation, responsible for determining the signal through the beta/gamma heterodimer to decide which event to trigger
- beta and gamma activation is based on alpha subunit
- when GTP binds to it, beta and gamma become a heterodimer and create a downstream affect
3 types of alpha subunit
- G alpha s
- ultimate target is to activate adenylate cyclase enzyme - G alpha i
- when activated it is inhibitory, dec adenylate cyclase - G alpha q
- when activated, inc levels of phospholipase C (PLC)
38
Q
G alpha s subunit
A
- Inc cAMP
- Inc pKA
- Inc proteins
- Inc adenylate cyclase
- if G alpha s is activated, but pKA levels are bad for example, adenylate cyclase will not be triggered
- entire downstream effect must occur, 1 malfunction will shut down entire system
39
Q
G alpha i subunit
A
- Dec cAMP
- Pka - no change
- Proteins- no change
- Dec adenylate cyckase
- inhibitory of production
40
Q
G alpha q subunit
A
- PLC activates through the G alpha q subunit
- PLC hydrolyzes PIP2 and cleaves(cuts) it in half into DAG and IP3
- DAG(stays in the membrane) activates PKC which activates IP3 and allows it to bind to parts of the cell
- IP3 binds to the endoplasmic reticulum’s receptor and calcium is released
- To increase calcium production, calcium binds to calmodulin
- Downstream effects increase
- if mutation occurs at PLC, calcium will never be secreted
41
Q
Kidney Structure
A
- comprised of a million nephrons
- nephrons are the functional unit of the kidney
- Kidney has a medulla (inner portion) and cortex (outer portion)
- Nephrons that go from the cortex to the medulla are called cortical medullary nephrons
- Nephrons that stay only in the cortex are called cortical nephrons
- the longer the Loop of Henle, the better the ability to reabsorb water
42
Q
Nephron Structure
A
- Bowman’s Capsule
- PCT (proximal convoluted tubule)
- dLOH (descending loop of henle)
- aLOH (ascending loop of henle)
- DCT (distal convoluted tubule)
- nephron ends here and connects to the collecting duct
- main target for ADH (kidneys receptor for ADH is on the nephrons)
- collecting duct are the last chance to reabsorb water before excreted from the body
43
Q
Why is it necessary for molecules to filter through a nephron before being secreted?
A
- because molecules are pressed out using pressure only
- a glomerulus is a ball of blood vessels
- it goes in afferent and leave efferent
- glomerulus pressure causes molecules to be pushed out
- > water, ions and nutrients
- > Glomerulus uses pressure to push molecules into Bowman’s Capsule using just force, not selective
- nephron determines regulates what is reabsorbed and what is secreted, determines what the body needs
44
Q
2 Types of Cells in the Glomerulus
A
- Macula Densa Cells
- Juxtaglomerular Cells (afferent mainly)
- together they form the juxtaglomerular apparatus
- contains cells that detect chemicals and pressure
- measure afferent and efferent flow
45
Q
Blood pressure affect at level of the kidney
A
- exerts affect on blood vessels
- we have stretch receptors that let us know what type of blood vessels we have
- if increase water reabsorption, sodium follows(uptake), inc blood pressure (and vice versa)
- if increase sodium, water follows(uptake), and blood pressure increases
- Hormones can also play a role in the inc of blood pressure
- > if inc ADH levels, inc water reabsorption, inc sodium uptake and as a result blood pressure will increase
46
Q
Epithelial Cells on Nephron
A
- very stable/organized in a group setting
- form apical (top) or basal (bottom)
- basal side adheres to the basement membrane/extracellular matrix and has a blood vessel underneath
- form a sheath and attach to each other via proteins
- selectively permeable (channels->aquaporins)
- if did not function properly anything in Bowman’s capsule would be secreted through urine
47
Q
Where absorption occurs in nephron and what type
A
- DCT = permeable to H2O and solutes
- dLOH = permeable to H2O only
- aLOH = permeable to solutes only
- PCT = permeable H2O and solutes
- Collecting Duct = permeable to H2O only
- at top near DCT and PCT it is diluted
- at bottom of loop of henle it is concentrated bc reabsorbed water in dLOH
- reabsorption is coming out of nephron into blood vessel
48
Q
Primary effect of ADH at the level of the kidneys
A
- to increase the permeability of water in the collecting duct and DCT
- > will result in smaller volume of urine that is more concentrated
- without ADH we would urinate constantly!!! - ADH has an effect on vascularizing blood vessels, inc blood pressure
- if an animal has a major wound, increase ADH to vascularize the blood vessels
49
Q
Glomerulus Filtrate
A
- what is filtered out of glomerulus into Bowman’s capsule
- H2O and solvents(nutrients and ions)
50
Q
Where does the majority of water reabsorption occur?
A
- 10% of water reabsorption occurs in the collection duct
- the majority, 90% of water reabsorption occurs in LOH, DCT and PCT
51
Q
Aquaporins in Nephron
A
- aquaporins are channels specifically for water
- CD is under influence of ADH and that is how we adjust the last 10% of water reabsorption for our needs
- AQP 1, AQP 2, and AQP 3/4
1. AQP 1 inserts itself on basal and apical sides of epithelial cells in the DCT, PCT and LOH - not under hormonal control, constitutively expressed (allows reabsorption of water in these areas)
2. ADH binds to G-alpha-s receptor on basolateral side of epithelial cell in collecting duct, causes activation of G-alpha-q receptor
3. G-alpha-q causes downstream effects that result in the phosphorylation of another water channel
4. AQP2 is inserted on apical side of epithelial cell in CD and is under hormonal influence - causes presence of AQP 3/4 through phosphorylating events
5. AQP 3/4 is inserted on basal side of epithelial cell in CD and is not under hormonal influence
52
Q
Macula Densa Cells and Juxtaglomerular in Vasoconstriction
A
- Macula Densa Cells are chemoreceptors and determine levels of solvents in a blood vessel (primarily sodium)
- Juxtaglomerular Cells are osmoreceptors and determine stretch coming in and out of the the glomerulus
- very sensitive
53
Q
What happens when blood volume decreases by 10% or more? What happens when blood pressure decreases by 10% or more?
A
- When blood volume decreases by 10% or more, will release ADH
- When blood pressure decreases by 10% or more, juxtaglomerular cells will produce renin
- liver will produce angiotensinogen
- renin will convert angiotensinogen to angiotensin 1
- liver will produce its own enzyme to convert angiotensin 1 to angiotensin 2
- angiotensin 2 binds to osmoreceptors (juxtaglomerular cells) and communicates need to regulate water uptake
54
Q
Disorders of ADH production
A
- If have dec in ADH release can be due to a tumor in the hypothalamus or the posterior pituitary gland
- If have Excessive inc in ADH release can have same problem as 1
- Diabetes insipidus
- always thirsty, can not quench thirst
- can be a mutation in ADH - Mutation in AQP3/4 will allow them to absorb water through AQP1
- can be a defect in the CD or a problem with the brain
- will alter ability to regulate the last 10% of water uptake
55
Q
TSH (thyroid stimulating hormone)
A
- produced as a result of TRH binding to thyrotroph
- binds to G alpha s receptor on basolateral side of follicle cell of the thyroid gland, produces T3, T4 and calcitonin
- regulates the thyroid gland
56
Q
Thyroid hormone production steps
A
- TSH binds to the receptor G alpha s on the basolateral side of the follicular cell
- Sodium (Na+) and Iodide (I-) travel from the blood stream into the follicle cell through a sodium-iodide symporter using active transport
- Nucleus of the follicle cell secretes the protein thyroglobulin
- Next step is the oxidation of iodide (I-), iodide moves from the basolateral side to the apical side of the follicle cell and becomes molecular iodine (I2) in the presence of the enzyme thyroid peroxidase (TPO). It then moves into colloid region and binds to thyroglobulin
- As more TPO is input into the colloid region the thyroglobulin binds with the iodine and iodinization will occur. Forms T1(MIT), T2 (DIT), T3 (TIT), T4 (Thyroxine)
- The thyroid hormones in the colloid must return back to the blood stream to reach their target organs
- T3 and T4 are packaged into secretory vesicles and brought back into the follicle cell
- T1 and T2 have no biological activity and are endocytized back into the follicle cell
- will pull Iodine off of the thyroglobulin in the follicle cell and push it back into the colloid to start the process again
- T3 and T4 are exocytized from follicle cell into blood stream
- T3 and T4 in the blood stream is 80-90% T4 and a much smaller percent of T3
- T3 is very biologically active and very potent
- T4 is not biologically active
- can not go from T1-> T2->T3-> T4 unless in the colloid with the presence of TPO, but in the body deiodinization occurs and goes from T4->T3->T2
- can take off iodines on thyroglobulin in periphery, but not put on
57
Q
Diseases of the Thyroid Gland
A
- both autoimmune diseases
1. Graves - hyperthyroidism
- 8x more common in women than men
- overactive thyroid gland, causes weight loss
- increased basal metabolism
- antibodies bind to the TSH receptor and act as an agonist with very high binding affinity
- drives TSH to continue producing excess T3 and T4
- leads to increased size of thyroid gland (Goiter)
- can cause bulging eyes, eyelids will retract and eyes protrude out
2. Hashimoto - hypothyroidism
- TG is not active enough, causes weight gain
- does not produce enough Thyroid Hormones
- > administer exogenous T3 and T4 to level out the thyroid
- more common in women
- a patient lacks Thyroglobulin, Thyroid Peroxidase and the products for production of TSH
- if occurs in utero (for dev fetus) can cause severe mental retardation and decreased development
58
Q
Levels of T3 and T4 in the blood stream
A
- 40x more of T4 is released into the blood stream than T3
- this is because T3 has a 100x higher binding affinity and is much more potent
- in the blood stream 80-90% is T4
- T3 is very biologically active and very potent
- T4 is not biologically active
- In the periphery, as the structure moves towards the target tissue T4 will be converted to T3 by deiodinase enzyme
- can take off iodines on the thyroglobulin in periphery, but not put on
- > deiodinization to T3 will cause a downstream affect and become T2 which is biologically inactive
59
Q
Wolff-Chaikoff Effect
A
- there is a peak in iodide in the blood stream
- the thyroid gland auto-regulates to fix it
- excess iodide inhibits thyroid hormone synthesis by inhibiting Thyroid Peroxidase production
- down-regulation of the sodium iodine symporter allows for iodide levels to dec
60
Q
Types of deiodinase enzyme involving Thyroid Hormones
A
- Type 1 deiodinase
- function to produce T3 in the liver, kidney, and thyroid gland for release into circulation
- vital for conversion from T3 to T2
- converts T4 to T3 and provides negative feedback - Type 2 deiodinase
- expressed in thyroid, placenta, brain, pituitary gland skeletal and cardiac muscle
- also in BAT (brown adipose tissue)
- negative feedback - Type 3 deiodinase
- in pregnant woman vital for communication with placenta
- maintains placental thyroid hormone activity for developing fetus
- in other words, placenta has their own deiodinase enzyme
61
Q
T3 Hormone receptor
A
- T3 receptor is located in the nucleus
- Heat Shock Protein (HSP) is dissociated from T4 and deiodinization will occur
- T3 will then be translocated into the nucleus and bind to the promoter region inside of the nucleus
- transcription of genes will occur and cause downstream effects
62
Q
Thyroid Gland
A
- is a plexus for massive blood supply with a lot of branching of blood vessels, provides many routes
- innervated by nerves that extend through the ganglia (collection of cell bodies in the PNS)
- > comes from the cervical region (neck)
- primary function is glucose lipid metabolism and energy
- > liver, pancreas, skeletal muscle(Bone), WAT/BAT(fat), Cardiovascular(heart), hypothalamus/pit (brain)
- all under regulation of TSH
