Exam 1 --Pt1 Intro to Endocrinology Flashcards
What is the endocrine system?
the system of ductless glands that synthesize and secrete chemical messengers (hormones) carried to target tissue by the blood
The endocrine system is tightly coupled to what other system? And what are the both sometimes called together?
the nervous system
called the “neuroendocrine system”
What are some of the chemical messengers that interact with one another and coordinate cells, tissues, and organs, to maintain homeostasis?
- NT (neuropeptides)
- endocrine hormones
- neuroendocrine hormones
- paracrines
- autocrines
- cytokines
What two glands secrete their hormones primarily in response to neural stimuli?
the adrenal medulla (primarily NE) and pituitary gland
Where are the three places that hormonal receptors are located?
- in the cell membrane (for peptide hormones)
- in the cell cytoplasm (for steroid hormones)
- in the cell nucleus
What body functions do hormonal systems play a key role in regulating?
- metabolism
- growth and development
- H2O and electrolyte balance
- reproduction
- behavior
What are the three levels that hormones act at?
- Whole body level
- Molecular level
- cellular level
At the Whole body level, what do hormones regulate and integrate?
- ionic and fluid balance
- E balance (metabolism)
- coping with env.
- growth and development
- reproduction
At the molecular level, what do hormones regulate?
- gene transcription
- protein synthesis and degradation
- enzyme activity
- protein conformation
- protein-protein interaction
At the cellular level, what do hormones regulate?
- cell division
- differentiation
- apoptosis
- motility
- secretion
- nutrient uptake
What is a classical hormone?
one secreted by tissue, picked up by blood, and transported to other tissue
What are three general classes of hormones?
- Proteins and polypeptides
- Steroids
- Tyrosine derivatives (biogenic amines)
Anterior and posterior pituitary hormones, insulin and glucagon, parathyroid hormone, and many others are examples of what class of hormones? Where are they stored in the cell?
proteins and polypeptides; stored in secretory vesicles until needed
What is the precursor for all steroid hormones? Where are they stored? What are two examples?
cholesterol; they are NOT stored; Ex: cortisol and aldosterone
What are three examples of Tyrosine derivatives?
- dopamine
- thyroxine (T4)/ triiodothyronine (T3)
- Norepinephrine/ epinephrine
T/F. Onset of hormone secretion after stimulus is the same for all locations.
False
What does the Adrenal medulla secrete (and it what ratio) and is it fast or slow?
epinephrine/NE in a 80:20 ratio; and it is rapid, w/in seconds
How long does the effect take for Pituitary and Thyroid hormones?
it is slower, and may take months for full effect
T/F. The concentration of hormones required for most functions is very large.
False–the conc. needed is usually very small; therefore rates of secretion are extremely small
What type of feedback prevents over-activity of hormonal systems? What are the two variables that could be used to control this?
negative feedback; controlled via secretory rate or degree of activity of target tissue
What levels can Negative feedback occur at?
- gene transcription
- gene translation
- steps in processing hormones
- steps in releasing stored hormones
What is positive feedback control of hormones and give an example?
ass. with surges of hormone; Ex: Luteinizing hormone ass. with ovulation
What is an example of a hormone ass. with a Diural cyclical variation ?
(diurnal = daily or circadian)
Growth hormone
What is a gland and hormone involved in a seasonal cyclical variation?
(seasonal = circannual)
Pineal gland–> melatonin effect on reproduction in seasonal breeders (shuts down reproduction)
What type of activity usually governs hormonal release and cyclical variation in hormone secretion?
due to changes in neural activity
What type of hormones are water soluble and how are they transported?
Peptides and catecholamines; dissolve in plasma and transported from sites of synthesis to target tissue where diffuse out of capillaries–> ISF–> cells
What hormones circulate through blood by being primarily bound to plasma proteins? Example?
Steroid and thyroid hormones; (<10% exists free in solution)
Ex: 99% of T4 in blood is bound to plasma protein
How is the clearance of steroid and thyroid hormones affected due to being bound to plasma proteins? How do they get across capillaries?
greatly slows clearance of these hormones; serves as reservoirs; have to dissociate to diffuse across capillaries
What two things will affect the hormonal concentration?
hormonal secretion and hormonal removal
What is the “equation” for hormonal concentration?
= rate of secretion - rate of clearance
if rate of secretion > rate of clearance = conc. increases
if rate of secretion < rate of clearance = conc. decreases
What is the “equation” for the Metabolic clearance rate (MCR)?
= rate of disappearance of hormone from plasma/ conc. of hormone
What are four ways in which hormones are “cleared” from plasma?
- metabolic/enzymatic degradation by the tissue
- binding with the tissues
- excretion by the liver into the bile
- urinary excretion by the kidneys
Clinical Note: What disease can cause abnormally high levels of steroid hormones and why?
liver disease; b/c these hormones are conjugated mainly by the liver and excreted in the bile
Where are the 3 locations where hormonal receptors are located?
- in/on the surface of the cell membrane
- in the cell cytoplasm
- in the cell nucleus
~# and sensitivity of hormone receptors are regulated
What are four intracellular signaling pathways, after receptor activation?
- ion channel-linked receptors
- G protein-linked receptors
- enzyme-linked receptors
- intracellular receptors and activation of genes (for steroids)
~1-3 are primarily protein receptors
What are second messengers?
- they are mechanisms for mediating intracellular hormonal function
- allow hormones that can’t cross the cell membrane (proteins/peptides) to affect intracellular fxns/processes
- create signal amplification
What are four cell membrane receptors ass. with second messengers?
- Adenylyl Cyclase- cAMP
- Phospholipase C mechanism (IP3/Ca++)
- Calcium-Calmodulin
- Enzyme linked receptor
Describe the way the Ca++ - calmodulin pathway works in smooth muscle.
Ca++ and calmodulin can combine and active MLCK–> will phosphorylate stuff and muscle contracts
Myosin phosphatase will dephosphorylate stuff and muscle relaxes
What is the most common 2nd messenger pathway for mechanism of action of protein/peptide hormones?
What is second most common?
Adenylyl Cyclase (cAMP)
Phospholipase C (IP3/Ca++)
What are the general steps for the Adenylyl Cyclase-cAMP pathway? (MC second messenger pathway)
Hormone binds to receptor on cell surface that is coupled with G protein –> alpha subunit binds and activated adenylyl cyclase–> which converts ATP into cAMP–> cAMP activates PKA–> which phosphorylates proteins and causes physiologic actions
What inactivates cAMP (adenylyl cyclase)?
phosphodieesterase (which would stop the phosphorylation rxn and therefore the effect of the hormone)
What are the general steps for the Phopholipase C (IP3/Ca++) pathway? (2nd MC second messenger pathway)
Hormone binds to receptor on cell surface–> HR complex coupled to Gq protein–> alpha-q–GTP complex migates w/in cell membrane and binds to and activates phospholipase C –> which frees IP3 and IP3 cuases release of Ca++ from ER–> Ca++ and diacylglycerol activate PKC–> which phsophorylates proteins and causes physiologic effects
What do the Adenylyl cyclase (cAMP) and Phospholipase C pathways have in common? In other words, what is important for hormonal response?
they both require phosphorylation in order for the hormone to exert their effect
What do 2nd messenger systems allow for that is significantly important?
signal amplification
What are two hormones that can cross the membrane and act directly on genes? And what do they do?
- Steroid hormones – increase protein synthesis
2. Thyroid hormones – increase gene transcription in nucleus
What is the pathway for Steroid hormones acting directly on genes?
- Steroid hormone binds to receptor in cytoplasm
- H-R complex diffuses OR is transported into nucleus
- binds to DNA–> transcription–> mRNA
- mRNA diffuses into cytoplasm where translation occurs at ribosomes to form protein
What is the pathway for Thyroid hormones acting directly on genes?
- T3 and T4 bind directly to receptor proteins in nucleus
- form many intracellular proteins (many are enzymes) - once bound to intranuclear receptors, can express control for days-weeks
Glucocorticoids, estrogen, progesterone, testosterone, aldosterone, 1,25-Dihydroxycholecalciferol, and T3 and T4, are all what type of homrones?
steroid hormones
~recall: precursor = cholesterol
GH, insulin, leptin, prolactin, vascular endothelial growth factor, hepatocyte growth factor, and fibroblast growth factor, are all what type of hormone?
require Tyrosine kinase
What two hormones fall under the category of using Guanylyl Cyclase (cGMP)?
- Atrial natriuretic peptide
- Nitric oxide
What three things influence the magnitude of hormonal responses?
- Conc. of hormone at target cell membrane
- Sensitivity of target cell to hormone
- Number of functional target cells
What 3 things does the conc. of hormone at target cell membrane depend on?
- rate of secretion
- rate of delivery via circulation
- rate of degradation
What 4 things does sensitivity of target cell to hormone depend on?
- number of functional receptors
- receptor affinity for the hormone
- post receptor amplification
- abundance of available effector molecules
What three things influence the Duration of hormonal responses?
- Duration of hormonal availability
- Mode of production of cellular response
- Rapidity of onset of compensatory changes
When it comes to duration of hormonal availability what three things are taken into consideration?
- duration of secretion
- amount secreted
- half-life in the blood
What are two ways the rapidity of onset of compensatory changes are influenced?
- counteracting responses (insulin vs glucagon)
- receptor desensitization or down regulation (turn down # receptors)
What are two way to measure Hormones in blood?
- Radioiummoassay (RIA)
2. Enzyme-linked immunosorbent assay (ELISAs)
How is Radioimmunoassay (RIA) done?
- specific antibody to the hormone is produced
- radioactive labeled hormones
- hormone to be measured competes with labeled hormone for binding sites on antibody
- standard curve
What is the relationship between % of antibody bound with radioactive antibody to hormone in test sample of the RIA standard curve?
increase the amount of hormone, then decrease the amount of radioactive hormone
What are the advantages of ELISA?
- NO radioactive isotopes required
- easily automated
- cost effective
- accurate for assessing hormone levels
- method of choice for clinical labs
What can ELISA be used to measure and how is it done?
- can be made to measure any protein
- combines specificity of antibodies with sensitivity of simple enzyme assays
- Quantified with colorimetric or fluorescent optical methods
