L03, 04, 05 - Introduction to Endocrine System, their Physiological Actions, and their Regulation Flashcards
3 modes of endocrine signalling?
- Endocrine signaling: acts on distant target cells through bloodstream
- Paracrine signaling: secreted into extracellular region, acts on adjacent target cell
- Autocrine signaling (e.g. vasopressin): secreted into extracellular region, self- stimulate
what forms the endocrine system?
Glands
Hormones
Receptors
Compare the hormones released by adrenal cortex and medulla?
Adrenal cortex : mineralcorticoids
- Aldosterone
- Cortisol
- Androgens
Adrenal medulla: Catecholamines
- Epinephrine
- Norepinephrin
List the 3 chemical classes of hormones?
- Amino acid derivatives
- Peptide and protein hormones (>3 a.a.)
- Steroid hormones
Compare the half-life in blood between 3 chemical classes of hormones?
- Amino acid derivatives:
- Insoluble, with carrier protein = days (long)
- Soluble without carrier = mins (short) - Peptide and protein hormones (>3 a.a.):
- Soluble, no carrier = mins (short) - Steroid hormones
- Most bound to carrier protein = hours (long)
Compare the source of amino acid vs peptide vs steroid hormones?
- Amino acid = Derived mostly from Tyrosine and Tryptophan
- Peptide: synthesized in RER as precursor, often need posttranslational processing to activate
- Steroid: Derived from cholesterol
Compare the location of hormone receptors based on the chemical calss
- Water soluble hormones
โข Peptide and protein hormones
โข Repelled by lipid in the cell membrane
โข Bind to a receptor protein on plasma membrane»_space; cytoplasmic or nuclear response - Lipid soluble hormones
โข Steroid hormones
โข Diffuse through the plasma membrane and bind to a receptor protein inside the cell (usually transcription factor)
Describe the intracellular signal transduction mechanism for steroid hormones?
1) Steroid hormone bind to receptor = detach repressor* protein
2) Hormone/ receptor complexes dimerize to act as transcription factor
3) Receptor complex decrease in surface hydrophobicity* due to conformational change
4) translocate to nucleus, bind to Hormone Response Element* via DNA binding site of complex
5) Induce or repress gene expression
Compare the MoA of Tamoxifen and Raloxifene on estrogen receptors?
Depending on tissue type:
Tamoxifen = suppresses estrogen receptor ฮฒ activation»_space; recruits corepressor protein to decrease estrogen function
Raloxifene = activates estrogen receptor ฮฑ = recruits coactivator = more estrogen
Describe the mechanism of GPCRs to generate secondary messengers?
GPCR + ligand = undergoing dynamic conformational changes in the Transmembrane domain
> > Allow docking of intracellular signal molecule to activate associated G protein
e.g. allow swapping GDP for GTP to activate G proteins in intracellular domain
Compare the function of 3 types of Gฮฑ subunits in GPCRs?
- Gฮฑs โ stimulation leads to increase cAMP
- Gฮฑi โ stimulation leads to decrease cAMP
- Gฮฑq โ stimulation leads to activation of phospholipase C (PLC)»_space; calcium signaling pathway
Describe the mechanism of GPCR and G proteins after Vasopressin binding at collecting tubule?
Vp binds to extracullar GPCR domain
> > conformational change at transmembrane domain (3rd intracellular loop)
> > Gฮฑs*** stimulation, increase cAMP
> > Increase expression of AQP2 + Increase insertion of AQP2 onto apical membrane
Describe the functional structure of Enzyme-linked receptors?
Cytoplasmic domain:
- Either intrinsic enzyme activity
- Associated with enyzmes (e.g. Tyrosine kinase, tyrosine phosphatase, serine/threonine kinase)
Transmembrane domain: dimerize and trigger enzyme activity
Extracellular domain: bind ligand
2 downstream signalling pathways of Insulin signalling?
PI3K/AKT pathway: controlling metabolic effects of insulin
Ras/ERK pathway: controlling cell growth and differentiation induced by insulin
Explain how insulin receptors cause downstream signalling cascade?
insulin receptor = tyrosine kinase transmembrane signaling protein
Insulin binds to ฮฑ-subunit cause autophosphorylation of ฮฒ-subunit
> > allow docking of substrates (e.g. insulin receptor substrate 1 (IRS-1)
4 types of hormone-hormone interactions?
- Redundant effect
- Reinforcement effect
- Antagonistic effect
- Permissive effect
Give example of hormones with redundant effect?
Diff. hormones produce same effect = safe-guard physiological functions + synergy
e. g. Glucagon, epinephrine, cortisol act on liver to increase blood glucose level during fasting
* at different time-constants*
Give one example of hormone causing reinforcement effect across whole body.
Cortisol: whole body response:
- Proteolysis at muscles
- Lipolysis at adipose tissue
- Glyconeogenesis at liver
- Desensitize against insulin
> > > Increase blood glucose
Give one example of hormone causing reinforcement effect across one cell?
Aldosterone bind to mineralcorticoid receptor:
- Increase Na/K ATPase expression for Basal membrane
- Increase ENaC and ROMK expression on apical membrane
> > Na reabsorption + K secretion
Give example of hormones with antagonistic effects?
Insulin vs glucagon
Define hormone permissive effect?
One hormone control expression of receptor for another hormone
Give example of hormones with permissive effects?
Estrogen induce expression of Progesterone receptor in uterus
ยป proliferate + develop uterus endometrium for implantation
3 types of rhythms of hormone secretion?
- Pulsatile (e.g. insulin, GnRH)
- Diurnal (e.g. cortisol and melatonin)
- Cyclic (e.g. menstruation)
Explain how change in pulsatile secretion of GnRH cause different gonadotrophin release?
High frequency release = stimulate LH release from ant. pituitary
Low freq. GnRH = Stimulate FSH release from ant. pit.
3 different types of stimuli for controlling hormone secretion?
- Humoral: respond to extracellular fluid change/ blood-bourne chemicals
- Hormonal: trophic hormone cause release of another hormone
- Neural: nervous system directly stimulate endocrine glands to release hormones
Give one example of hormonal response triggered by change in the extracellular fluid?
secrete parathyroid hormone (PTH) in response to Ca2+ level in extracellular fluid:
High [Ca2+]: Ca2+ binds to activate calcium-sensing receptor = inhibits PTH secretion
Low [Ca2+]: Ca2+ not bound to receptor = no inhibition = PTH secretion to increase [Ca2+]
Describe how Pancreatic ฮฒ-cell respond to high blood glucose? think electricity
Pancreatic ฮฒ-cell: ATP-sensitive potassium channels are open at rest
- Glucose diffuses into cell through membrane glucose transporter»_space; glycolysis make ATP
- ATP-sensitive potassium channels close = no K+ efflux = depolarization
- Voltage-dependent Ca2+ channels open = increase intracellular [Ca] = insulin exocytosis
Describe how adrenal medulla responds to stress-induced sympathetic activation?
sympathetic nervous system
> > AP to chromaffin cells in adrenal medulla
> > neurons secrete Ach to nicotinic receptors of chromaffin cells
> > Trigger Tyrosine hydroxylase converts tyrosine to DOPA to NE
> > Exocytosis of catecholamines (norepinephrine / epinephrine) into capillary
Give one example of positive feedback hormonal response?
uterine muscle contraction during labor
> > nerve impulse to hypothalamo-pituitary axis
> > posterior pituitary releases oxytocin
> > uterus contracts more vigorously
Give one example of negative feedback hormonal response? think glucose
Negative feedback of glucose production by glucagon:
After restoring glucose level, glucagon secretion decreases
What are the 3 sub-categories of complex multilevel negative feedback systems? use hypothalamo-pituitary system as example
- Long loop (e.g. target organ to hypothalamus, target organ to anterior pituitary)
- Short loop (e.g. anterior pituitary to hypothalamus)
- Ultra-short loop (e.g. hypothalamus to itself)
Why is there the need for long loop, short loop negative feedback?
greater degree of fine-tuning of hormone secretion
Minimizes changes in hormone secretion when one component of the system is dysfunctional
Describe the feed-back inhibition of thyroid hormone release?
TRH from hypothalamus stimulate Ant. Pituitary to release TSH
TSH stimulate thyroid gland to release thyroid hormones
Increased thyroid hormone conc. = feedback inhibition on TRH and TSH release
Set-points in closed negative feedback hormonal control cannot be changed? T or F?
False
Set-point can be changed
e.g. Epinephrine can override the pre-determined set-point of blood glucose level
What is the function of feed forward hormone response?
Anticipatory response in the later stage of the pathway
to prevent large change in variabled
Give one example of feed forward control of hormones?
E.g. cephalic phase: sight, smell, taste of food
> > anticipate high blood glucose after meal
> > parasympathetic vagus nerve from brain to beta cells of pancreas
> > ACh acts on M3 receptor, signalling insulin release before even eating
3 types of control of hormone activity at the hormone/ receptor level?
1) Conversion of prohormone to active form
2) Regulation of hormone receptors: up-regulate/priming or down-regulate/ desensitization
3) Hormonal clearance by degradation
Describe the role of the renin-angiotensin system in regulating fluid levels?
- Liver releases angiotensinogen (= precursor) into blood
- Macula densa of kidney sense low [Na]»_space; juxtaglomerular cells secrete renin
- Renin convert angiotensinogen to angiotensin I
- ACE in pulmonary blood convert angiotensin I to angiotensin II
- Angiotensin II cause vasocontriction + release aldosterone from adrenal cortex to uptake Na in DCT
Describe the role of Deiodinase subtypes on T4 hormone function?
Different subtypes of Deiodinase are present at diff. tissue
Control of which subtype of deiodinase is released = control whether to activate or deactivate T4
Hormone-receptor interactions are limited by the number of receptors. T or F?
True
Biological effect is proportional to the amount of complex that forms
Give one example of hormone priming effect?
High frequency GnRH pulse can increase the sensitivity of its target cell (anterior pituitary cells) to further stimulation
Describe the mechanism of growth hormone receptor down-regulation?
After prolonged exposure to GH:
internalize/endocytose its own receptor-hormone complex for degradation
Decrease cell surface receptors = decrease sensitivity of cell
3 routes for hormone breakdown and elimination?
- Liver enzyme degradation, bile excretion
- Kidney enzyme degradation, urine excretion
- Breakdown inside target cell, endolysosomal degradation
List the degradation reactions for protein and steroid hormones?
Peptide hormones: proteolysis
Steroid hormones:reduction, hydroxylation, oxidation, decarboxylation,or esterification
Formula for metabolic clearance rate for any substance?
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Define primary, secondary and tertiary endocrine disorders?
Primary = Secretory gland problem e.g. tumors, infection
Secondary and tertiary = Endocrine feedback error (mostly hypothalamic-pituitary axis)
Principle of testing for endocrine disorders?
Stimulation / suppression testing
Excess hormone suspected = suppression test
Deficiency suspected = Stimulation test
Describe the dexamethasone suppression test at low or high dose? think primary or secondary endocrine disorder
Measure cortisol level next morning
- Low dose = Present or absent cushing syndrome
- High dose = -ve feedback on ACTH producing cells but not ectopic or adenoma making ACTH
ยป distinguish Cushing disease from cushing syndrome
Describe the captopril suppression test?
- Captopril suppress ACE = suppress aldosterone level
Test for primary aldosteronism (hypersecretion of aldosterone)
Describe the ACTH stimulation test and what it tests for?
Adrenal insufficiency = not increase cortisol after ACTH stim
ACTH stimulate cortisol production
If Pituitary hormone level is high, but target hormone is low. What is defective?
Primary disorder (target organ fails to produce / secrete hormone)
If Pituitary hormone level is low and Target hormone level is low. What is defective?
Secondary disorder (pituitary failure)
If Pituitary hormone level is high and target hormone level is abnormally high. What is defective?
Autonomous secretion of pituitary hormone (e.g. pituitary tumor); or
Resistance to negative feedback from target hormone
If pituitary hormone level is low but target hormone level is high. WHat is defective?
Autonomous secretion by target organ (e.g. tumor, primary hyperthyroidism)
