Intro to Endocrinology Flashcards
T/F Hormones can exert their effects on neighboring or distant targets.
True.
Where do endocrine glands secrete their products?
into the interstitium–>into circulation
Do endocrine glands use ducts?
No. they are ductless.
In a basic sense: what is the regulatory goal of the endocrine system?
homeostasis
What are some key roles of the endocrine system?
- Regulation of salt/water balance
- Regulation of blood volume/blood pressure
- Regulation of calcium & phosphate
- Regulation of energy balance
- Regulation of stress response
- Regulation of reproduction & development
- Regulation of growth
What are the 2 main categories of hormones that the hypothalamus secretes?
releasing hormones
inhibitory hormones
What are the 4 main releasing hormones that the hypothalamus secretes?
GHRH: growth hormone releasing hormone
CRH: corticotropin releasing hormone
TRH: thyrotropin releasing hormone
GnRH: gonadotropin releasing hormone
What are the 4 main inhibitory hormones that the hypothalamus secretes?
somatostatin
dopamine
vasopressin
oxytocin
What are the 7 main hormones that the pituitary gland releases?
Growth Hormone Prolactin ACTH: adrenocorticotropic hormone MSH: melanocyte stimulating hormone TSH: thyroid stimulating hormone FSH: follicle stimulating hormone LH: luteinizing hormone
What are the 3 main hormones released from the thyroid gland?
T3
T4
calcitonin
What is the main hormone released from the parathyroid glands?
parathyroid hormone
What are the 5 main hormones released from the adrenal glands?
Cortisol Aldosterone Adrenal androgens Epinephrine Norepinephrine
What are the 3 main hormones released from the pancreas?
insulin
glucagon
somatostatin
What are the 2 main hormones released from the ovaries?
estrogen
progesterone
What is the main hormone released from the testes?
testosterone
What are the 8 main places that hormones are secreted in the endocrine system?
Hypothalamus Pituitary Gland Thyroid Gland Parathyroid gland Adrenal Glands Pancreas Ovaries Testes
What are the 3 types of hormones?
steroids, amines, & peptides
What types of secretions in the body include ducts?
exocrine secretions, like packages of enzymes secreted thru ducts. this is NOT a part of the endocrine system.
What are the 3 types of hormone actions?
autocrine
paracrine
endocrine: acts at distant organs or tissues
What is an example of autocrine action of a hormone?
insulin inhibiting its own release
*this is where a hormone acts on the same cell that it was secreted from
What is an example of paracrine action of a hormone?
estrogen acting in the ovaries
*action in a neighboring cell
What is the usual pattern of hormone release in the endocrine system?
Hypothalamus: releases releasing hormone
Pituitary Gland: releases tropic hormone
Target Organ: releases effector hormone
**effector hormone goes to site of action
In the usual pattern of hormone release–>what acts to inhibit hormone release?
The effector hormone released from the target hormone will go back & inhibit the release of releasing hormone from the hypothalamus & tropic hormone from the pituitary gland.
What does thyroxine build up?
T3 & T4
ACTH released from the anterior pituitary acts on what? What does it release?
Acts on the adrenal gland.
Cortisol.
GH released from the anterior pituitary acts on what? What does it release?
Acts on the liver.
Causes the release of insulin-like growth factors.
TSH released from the anterior pituitary acts on what? What does it release?
Acts on the thyroid gland.
Releases thyroxine
FSH & LH released from the anterior pituitary act on what? What does this release?
Acts on the sex organs.
Releases estrogen, progesterone, testosterone
causes ovulation & spermatogenesis
Prolactin released from the anterior pituitary acts on what? What does this release?
Breasts
causes lactation
How do peptide hormones travel in the blood? What is the significance of this?
They travel free in the blood.
this means that they are more easily degraded.
How do steroid hormones travel in the blood? What is the significance of this?
They have to travel in the blood bound to something. A plasma transport protein, called globulins.
This means that they are protected from rapid degradation & clearance.
They are not active until they are free.
What are 4 examples of hormone-binding proteins? What do they bind to?
CBG: corticosteroid binding globulin
TBG: thyrotropin binding globulin
SHBG: sex hormone binding globulin
Albumin: non-specific binding
How does T4 travel in the blood? What is its half life? If someone is experiencing hypothyroidism…what are the implications of this for treatment?
T4 travels in the blood via TBG.
Its half life is therefore longer, 7 days.
**this means that a missed dose can be taken within the week.
How does PTH (parathyroid hormone) travel in the blood? What does this mean for its half life? What are the clinical implications of this?
It travels free in the blood. Its half life is 2-4 minutes, much shorter b/c it isn’t bound to a globulin.
Clinical Significance: you can measure your progress during surgery when removing a hyper functioning parathyroid tumor
Where are the receptor sites for hormones?
Either on the surface of the cell or inside the cell.
What are 3 common types of cell surface receptors?
G coupled transmembrane receptors (7 domains)
Tyrosine kinase receptor (single domain)
Ligand gated ion channels
What are some amino acid derived hormones that use the G protein mechanism?
epinephrine
norepinephrine
What are some peptide hormones that use the G protein mechanism?
Glucagon Angiotensin GnRH SS GHRH FSH LH TSH ACTH
Most _____ hormones use the G protein mechanism.
tropic
alpha i in the G protein mechanism causes what cascade to occur?
targets adenylate cyclase
causes cAMP to go down
alpha q in the G protein mechanism causes what cascade to occur?
targets phospholipase C
with the help of DAG & Ca++ it activates PKC
alpha s in the G protein mechanism causes what cascade to occur?
target adenylate cyclase
causes cAMP to go up
alpha12 in the G protein mechanism causes what cascade to occur?
targets RHOGEFs
causes an increase in RHO
whatever that means…
What type of a receptor does insulin use?
tyrosine kinase receptor
binding leads to phosphorylation & lots of activity!
What is the main effect of insulin binding tyrosine kinase receptor on a cell?
Glut 4 transporters are moved to the cell membrane so that glucose can move into the cell. This then leads to the metabolism & storage of glucose, the main effect of insulin.
What are some of the other effects that insulin has on a cell, aside from glucose transport?
cell growth
protein synthesis
glycogen synthesis
What is pseudohypoparathyroidism?
this is a defect in the G protein mechanism of the receptor for parathyroid hormone.
even with elevated levels of PTH, which patients have, there are symptoms of hypoparathyroidism.
How do you confirm a diagnosis of pseudohypoparathyroidism?
administer exogeneous PTH
measure the urine level of cAMP
**if they have the condition the cAMP should be low
How are intracellular nuclear receptors used?
they are sometimes used by second messengers of normal hormones that go to cell surface receptors…usu they are used by steroid hormones that diffuse thru the plasma membrane.
How does an intracellular receptor work?
it is in the nucleus.
the hormone or second messenger binds a receptor inside the cell
the receptor-hormone complex binds a HRE (hormone response element) on the DNA
alters gene expression
Overview:
what types of hormones bind cell surface receptors? What types of hormones bind intracellular nuclear receptors?
Cell Surface: peptide & amine hormones
Nuclear: steroid & thyroid
What type of hormone is Vitamin D considered?
a steroid hormone
Are thyroid hormones steroid hormones?
NO.
but thyroid hormones can diffuse thru the plasma membrane & they act like steroid hormones. They both use nuclear receptors.
Explain how peptide hormones are made & released?
Transcribed as pre-hormones. Undergo post-translational modification.
Stored in secretory granules.
Released by exocytosis
How do peptide hormones act once they are released?
They travel free in the blood w/o a carrier protein b/c they are hydrophilic. Thus, they have short half-lives. They bind to cell surface receptors & have their effect in the cell via second messengers.
What are some examples of peptide hormones?
Insulin Glucagon ACTH PTH FSH LH TSH HCG
What are some examples of glycoproteins that are peptide hormones?
FSH
LH
TSH
HCG
What are the 2 main classes of amino acid derived hormones? WHat are they derived from?
Catecholamines
Thyroid Hormones
**derived from tyrosine
Where are steroid hormones synthesized? What are they synthesized from?
Locations: adrenal cortex, gonads, placenta
synthesized from cholesterol
Once they are released, what do steroid hormones do?
They travel in the blood bound to a carrier protein b/c they are hydrophobic. Thus, they have longer half-lives.
They diffuse thru plasma membrane of target cell & they bind to the nuclear receptor.
What are the 3 patterns of hormone secretion?
Pulsatile
Episodic
Diurnal
What does it mean for a hormone to be released in a pulsatile fashion?
it is released in regular pulses varying in amplitude & frequency
What are some examples of hormones that are released in a pulsatile fashion?
GH: growth hormone
GnRH: gonadotropin releasing hormone
If you were treating someone who was infertile with a deficiency of Gonadotropin releasing hormone, how would you want to administer the exogenous GnRH? Why?
While it might be tempting to administer the GnRH continuously at high doses, this wouldn’t be wise b/c of how it is normally released.
Continuous release can cause desensitization for receptors that are used to hormones that are released in a pulsatile fashion. It would suppress FSH & LH.
Why is it important to sleep while you are growing up, especially?
b/c the most GH is released while you are sleeping!
Explain how diurnal secretions work.
These hormone secretions are based off of the sleep-wake cycle (circadian rhythm). There are low hormone levels at night that peak during the daytime.
**why jet lag & night shifts are difficult
What determines the circadian rhythm?
the hypothalamus
specifically: the SCN: suprachiasmatic nucleus
What is an example of a hormone that is released diurnally?
Cortisol
When is the best time to measure cortisol levels? Why?
If you suspect low cortisol levels, you must check them around 10AM b/c that is when they are naturally highest. If you check at nighttime–>of course they will be low!!
How does the dawn phenomenon relate to why patients with Diabetes can get a surge in fasting blood glucose in the morning?
We wake up w/ increasing hormone levels. This results in an increase in blood glucose. The body produces a bunch of insulin. Diabetics can’t do that so they get an elevated fasting blood glucose in the morning.
After hormones hit their target…what is next for them?
they go to the liver for metabolic transformation
they are excreted in the urine
What are the 3 forms of regulation of hormonal release?
hormonal
nutrient/ion regulation
neural
what does hormonal regulation of hormone release entail?
this includes tropic hormones & feedback loops
What does negative feedback require?
a closed loop system: product, effect, sensor
What is the common example of positive feedback?
oxytocin: important in delivery & lactation
* with the presence of the head in the birth canal–>more oxytocin is released
* with suckling of the baby–>more oxytocin is released
What are some examples of open loop hormones? Do they exhibit negative feedback?
Don’t exhibit negative feedback b/c it is an open loop!
Usu they involve the CNS, like Epi & Norepi.
Also includes peptide hormones that have a super short half life.
Once the storage of the hormone is depleted, it doesn’t get secreted anymore.
In primary hypothyroidism…what is lacking? How do you treat it?
the thyroid gland doesn’t make thyroxine
Well, the TSH levels are normal–>so you look @ those to decide how much fake thyroxine (levothyroxine) to give.
When you treat primary hypothyroidism…is it a closed loop or open loop system?
Open Loop. No more feedback. Now, the endocrinologist is trying to maintain homeostasis.
What’s the basic idea behind hormone measurement?
often it is measured in the blood or the product of the hormone is measured in the blood
**super important for diagnosis
What is the ACTH stimulation test? What is it used to diagnose?
Used to diagnose adrenal insufficiency
Give a bunch of exogenous ACTH.
Watch whether the adrenal gland produces a bunch of cortisol.
If not, something is wrong.
What is the dexamethasone suppression test? What is it used to diagnose?
Give dexamethasone to a patient that you suspect has Cushing’s disease (excess cortisol).
This should inhibit the hypothalamus & pituitary gland. You measure cortisol levels. If they are high, that means that the adrenal gland is still releasing a ton of cortisol. Maybe Cushing’s.
Radioimmunoassay (RIA) is a way of measuring hormone levels. Explain it in basic terms.
mix radio-labeled hormone w/ antigen so that they bind. Put in patient’s hormones to compete with the glowing hormone. Measure the radioactivity & using a Scatchard plot you kind of get an idea of hormone levels.
What’s the difference b/w ELISA & RIA in measuring hormone levels?
ELISA doesn’t use radiation to measure bound hormone, but enzyme catalyzing color change.
What is something that can lead to errors in measuring hormone levels w/ RIA & ELISA?
cross-reactivity of hormones
other hormones can bind to the same receptor–>you think oh, i have this amount of hormone X. But actually you have that amount of hormone X & hormone Y or something.
What is a clinical example of the importance of cross-reactivity of hormones?
When women are first pregnant they can sometimes exhibit hypothyroidism. This is b/c their higher levels of hcG compete for the thyroid receptors…Gone after 1st trimester.
What is the hook effect? How does it relate to hormone measurement w/ assays?
there is so much hormone, that the receptors are saturated. Looks like there are relatively normal levels of the hormone, but there is a LOT more. You need to dilute the sample to fix this measurement problem.
So, if you get a patent’s hormone levels. How do you know if they are normal/healthY?
You compare it to reference ranges. This is the range that includes 95% of normal people & what their levels are. But…if someone is outside of the reference range, might not be a problem–>theoretically they could be a part of the normal 5%.
So…if a woman comes in after removing an adenoma from her pituitary gland…and she exhibits symptoms of hypothyroidism…what should you check?
Check TSH. If that is normal…don’t stop b/c you are only focused on the pituitary gland!
Check the thyroid!
What are the 3 basic categories of endocrine disorders?
Hormone Deficiency
Hormone Resistance
Hormone Excess
What are some examples of endocrine disorders that have to do with hormone deficiency?
Type I Diabetes: autoimmune destruction of beta cells
Deficiency of a precursor, like lack of iodine–>can cause goiter (enlarged thyroid b/c it is constantly being hit w/ TSH to get high enough levels of thyroid hormones) & causes hypothyroidism.
What are some examples of endocrine disorders that have to do with hormone resistance?
Type II Diabetes: insulin resistance
Pseudohypoparathyroidism: receptor mutation
What are some examples of endocrine disorders that have to do with hormone excess?
Acromegaly: tumors/mutations
Grave’s disease: autoimmune activation
