Endocrine Intro Flashcards
“senders” in endocrine system
endocrine pancreas, parathyroid glands, pituitary gland, thyroid, adrenal, gonads, placenta
Endocrine System
communication system
“messages” of endocrine system
hormones
Functions the Endocrine System Controls
BP, Blood Volume, ECF [electrolyte], RBC production, Blood [Glucose], Growth & Maturation, Repro, Behavior, Immunomodulation, Senescence
Homeostasis maintained by..
Nervous system, immune system, endocrine system
Why study the endocrine system?
to better understand endocrine diseases, non-endocrine diseases, and how to use hormones as therapies
non-endocrine diseases cause problems via
inappropriate hormone release
Hormone
substance that travels through blood to cause specific response at site OTHER THAN where it was made
Endocrine Hormone Conveyance
Bloodstream
Neurotransmitter conveyance
axonal (ie norep)
Neuroendocrine conveyance
bloodstream and axonal
ie. norep
Paracrine hormones effect
neighboring cells
Autocrine hromones effect
the cell that secreted it
Endocrine hormones effect
various target organs at other locations
Paracrine hormones secreted into
ECF
Autocrine hormones secreted into
ECF
Endocrine hormones secreted into
bloodstream
Hormones can be…
paracrine, autocrine or endocrine
ex: insulin
Insulin’s paracrine effects
inhibit glucagon secretion by alpha cells
Insulin’s autocrine effect
regulates growth and function of beta cells
Insulin’s endocrine effect
glucose uptake for systemic organs
3 Classifications of Hormones
- Proteins
- Steroids
- Amines (‘exceptions’)
Amines are
tyrosine derivatives.
“exceptions”/”hybrids of steroids & proteins”
-catecholamines & thyroid hormones
Protein Hormone Structure
chains of specific amino acids
Protein/Peptide Solubility
hydrophilic
Protein/Peptide Synthesis
rough ER and packaged in Golgi
Protein/Peptide Storage
cytoplasmic secretory granules
Clinical significance of protein/peptide storage in granules
can’t regulate synthesis but can regulate release etc.
Protein/Peptide Secretion
exocytosis of granules
Protein/Peptide Transport in Blood
unbound, free hormone
Protein/Peptide Receptor Site
surface of target cell b/c can’t pass through alone
Protein/Peptide Mechanism of Action
channel changes or activation of 2nd messenger systems
Protein/Peptide Hormones
include those made in hypothalamus, pituitary, pineal, pancreas, parathyroid, GIT, liver, kidneys, heart
Protein/Peptide Half-Life
short!
Protein/Peptide Clearance
- small mount of small proteins in urine (degraded in kidney)
- endocytosis of receptor-hormone complexes & lysosomal degradation
Protein/Peptide Route of Administration
injection! b/c it’ll be degraded in GI w/ other proteins you eat
Steroid Hormone Structure
cholesterol derivative
Steroid Hormone Solubility
hydrophobic (lipophilic)
Steroid Hormone Synthesis
ovaries, testes, placenta, adrenal CORTEX
Steroid Hormone Storage
not stored in cell (cholesterol precursor is stored), meaning we can regulate their synthesis
Steroid Hormone Secretion
can cross cell membrane
Steroid Hormone Transport in Blood
bound to transport proteins, albumin
Steroid Hormone receptor site
inside a target cell b/c don’t need a receptor outside the cell
Steroid Hormone Mechanism of Action
alters gene expression
Steroid Hormone Types
progestins, androgens, estrogens, testosterone, minceralocorticoids (aldosterone), glucocorticoids, active Vit. D
Steroid Hormone Half-life
long!
Steroid Hormone clearance
liver and kidney
Steroid Hormone Route of Administration
can give orally b/c they’re lipids
Why are Steroid Hormone half lives so long?
because they’re bound to transport proteins which inactivates them and makes them harder to break down
Types of Amine Hormones
- Catecholamines
2. Iodothyronines
Catecholamine Structure
tyrosine derivative
protein like
Catecholamine Solubility
hydrophilic
Catecholamine synthesis
adrenal MEDULLA or neurons
Catecholamine storage
cytoplasmic secretory granules
Catecholamine secretion
exocytosis of granules
Catecholamine transport in blood
unbound or loosely bound to albumin
Catecholamine receptor site
surface of target cell
Catecholamine mechanism of action
channel changes or activation of 2nd messenger systems
Catecholamine types
epinephrine, norepinephrine, dopamine
Catecholamine half-life
short
Catecholamine clearance
uptake (w/ receptor into cell), enzymatic conversion
Catecholamine route of administration
injection
Iodothyronines structure
iodinated tyrosine derivative
steroid-like
Iodothyronines solubility
hydrophobic (lipophilic)
Iodothyronines synthesis
thyroid
Iodothyronines storage
in thyroid as colloid, acts as a reservoir
Iodothyronines secretion
can cross cell membrane
Iodothyronines transport in blood
bound to transport proteins (TBG) & inactive when bound, and to albumin
Iodothyronines receptor site
inside target cell
Iodothyronines mechanism of action
alters gene expression
Iodothyronines types:
T3, T4
Iodothyronines half-life
long (relatively speaking) with species differences
- in dog, T3 = 6 hrs, and T4 = 10-16 hrs
- in ppl, T3 = 6 hrs, and T4 = 7 days
Iodothyronines clearance
deiodination, liver & kidney
Iodothyronines route of administration
can give orally
Endocrine Axis (cascade)
stress signal -> hypothalamus -> hormone released -> pituitary gland -> tropic hormone released -> peripheral endocrine gland -> hormone (cortosol +) released -> hormone goes to target organ - physiologic effect
Negative feedback in endocrine system
occurs from [HORMONE] not physiologic response
Patterns of secretion
circadian, ultradian, seasonal,
-some pituitary hormones are secreted in PULSE that cycle every 2-20 min (esp protein ones)
What determines patterns of hormone secretion?
genetically encoded or acquired.
circadian rhythms
once daily
endogenously generated by cues like light, feeding, activity, sleep
ultradian rhythms
occurs multiple times a day
(diurnal rhythms are day-night)
seasonal rhythms
control breeding, hybernation, & migration behaviors
The types of secretion patterns and knowing which hormones are pulsatile and important to know because
hormone levels can help us diagnose but we need to know these levels change throughout the day
Relative Plasma Concentrations of Hormones
Cortisol and ADH (Vasopressin) are present in very low amounts and still can cause big effects
Lipid Soluble Hormones (steroids and thyroid hormones) & entering cells
must dissociate with plasma protein to enter cells
protein bound lipid soluble hormones serve as
a RESERVOIR to replenish free hormone when it enters a cell & binds to receptor
Methods of Hormone Clearance
- metabolism in tissues
- binding in tissues
- excretion by liver (bile)
- excretion by kidney (urine)
Hormone Clearance
“cleaning the plasma”
rate of removal of hormone from the blood
Hormone receptors
- VERY SPECIFIC for one and only 1 hormone
- the amount changes constantly
Ligand-Receptor Interaction
- one hormone binding to one receptor can cause enough amplification of signaling to achieve maximum effect
- one hormone-receptor binding can activate MULTIPLE pathways & cause multiple effects
Peptide Hormones and Catecholamines
act as extracellular signals generating altered cellular processes
Steroid hormones and Iodothyronines act
as intracellular signals and change gene expression
Hormone Receptor Types
- Ion Channel-Linked
- G Protein-Linked
- Enzyme-Linked
- Intracellular
Ion channel-linked receptors
open or close an ion channel when activated
G Protein-Linked Receptors
- activated receptors cause activation of a G protein in cell membrane which initiates intracellular signals leading to physiologic effect
- G proteins can be stimulatory or inhibitory
Enyzme-Linked Receptors
when activated, function directly as enzymes
Intracellular Receptors
located in cytoplasm or nucleus & when activated cause protein synthesis or gene transcription
After a receptor is activated,
the second messenger systems are activated
Types of 2nd Messenger Systems
Adenylyl Cyclase-cAMP
Cell Membrane Phospholipid
Caclium-Calmodulin
Adenylyl Cyclase cAMP Steps
- Hormone binds to G protein-linked receptor
- Stimulatory G protein activates adenylyl cyclase
- Adenylyl cyclase converts ATP to cAMP
- cAMP activates enzyme cascade in cell
- Cell’s response to hormone is achieved
(opposite for inhibitory G protein from Steps 2-5)
Cell Membrane Phospholipid Steps:
- Hormone binds to enzyme-linked receptor
- Phospholipase C is activated
- Phospholipase C catalyzes breakdown of membrane phospholipids into IP3 and DAG
- IP3 mobilizes Ca2+
- DAG activates Protein Kinase C which activates many proteins
- Cell’s response to hormone is achieved by steps 4 & 5
(how a receptors work)
Calcium-Calmodulin Steps as 2nd Messenger:
- Hormone binds to ion channel-linked receptor (or voltage channel opens ion channel)
- Ca enters cell & binds to Calmodulin
- Calmodulin activated
- Calmodulin activates/inhibits protein kinases
- Cell’s response to hormone is achieved.
What influences receptor expression numbers on a cell
- genetically controlled expression
- other factors (disease, ligand binding, etc) that alter sensitivity of cell by altering number of expressed receptors
- tissue type
Pathologic Up regulation of receptors
adrenergic receptors in hyperthyroidism
Pathologic Down regulation of receptors
insulin receptors in Type 2 Diabetes
Decreased responsiveness
decreased response at same CONCENTRATION as normal response
Normal response
gives maximum response with hormone concentration
decreased sensitivity
same response at a HIGHER concentration than normal
