Endocrinology (1) Flashcards
proof of hormones the system process of Renin-angiotensin-aldosterone system function of angiotensin II inhibitors hormonal system hormone family and its interaction with receptor measuring levels of hormones secretion of hormones regulation of systems
secretin - discovered
by William Bayliss and Ernest Starling
1st hormone
secretin tested - neuronal
isolate gut from nervous system by cutting nerves to gut and add acid to duodenum = there was secretion
therefore not neuronal
secretin tested - chemical and results
stop blood flow from gut to general circulation and repeat with acid = no secretion
therefore acid on intestines release agent - carried to pancreas through circulatory system
isolate agent and purify = secretin
endocrine system - function and uses
group of cells releasing signal into circulatory system at low conc
carried around the body to target
manipulating system/modifying intracellular signalling pathways
main regulators for homeostasis
endocrine, parasympathetic and sympathetic nervous systems
field in pharmacology
regulate blood pressure, cell growth, cancer studies, diabetes or control blood sugar and ion levels
example of pharmacology
Renin-angiotensin-aldosterone system
reducing blood pressure
renin-angiotensin-aldosterone system to increase BP
decrease in blood pressure = decrease in flow of fluid through tubule to kidney allow cells to absorb
low in sodium due to absorption back into body monitored by glomerulus - juxtaglomerulus system
decrease in BP = decrease in sodium
renin-angiotensin-aldosterone system - renin
cleaves angiotensin = angiotensin 1 - carried in blood to capillaries in kidney and lung
cleaved by enzyme ACE = angiotensin 2 - active hormone
renin
enzyme released in kidney induced by 2 things acting together in juxtaglomerular
function of angiotensin
affects brain bind to receptors in kidney regulate adrenal cortex of adrenal cortex of adrenal gland cause vasoconstriction of BV regulate production of ADH
affecting the brain
for angiotensin
nerve regulation - sympathetic activity increases
receptor binding - angiotensin
in tubule - increase NaCl absorption and excretion of K - not 1:1 - NaCl absorbed more = ionic imbalance - transfer of water with NaCl and absorb water
regulate adrenal cortex of adrenal gland - angiotensin
releases aldosterone
potentiates absorption of NaCl and loss of K
regulate production of ADH
vasoconstriction and affect collecting ducts part of kidney - allow pores to be put in
inhibitors - stop activity to decrease BP
renin ACE angiotensin 2 receptor aldosterone ADH
renin inhibitor
prevent digestion of angiotensinogen
ACE inhibitor
prevent cleavage of angiotensin 1
angiotensin 2 receptor inhibitor
prevent angiotensin 2 binding
aldosterone inhibitor
prevent aldosterone binding to receptor
ADH inhibitor
decrease BP - prevent water absorption and arteriolar vasoconstriction
receptor in hormonal system
highly specific
some have more receptors and some receptors bind to more than one hormone
hormonal - low Kd
high affinity
hormone released into whole blood system
Kd
how strongly they bind
to have effect in hormonal system
lots of integrated amplification at level of cell with receptor
protected transfer system
hormone bound to carrier protein
free hormones
bind to receptor - H-CPr must dissociate = H + CPr
hormone action continue for longer and regulate amount of free hormone
overall effectiveness depend on
conc of affinity of free hormone
no. receptor present on cell
efficiency of amplification
stop signalling - removed
3 main hormone family
Amine-derived
peptide
lipid and phospholipid
Amine-derived hormones
take off COOH from tyrosine and tryptophan decarboxylated = amine
e.g. catecholamines and thyroxine
peptide hormone
small TRH (3 a.a) and ADH/vasopressin 9a.a
protein hormone - insulin and growth hormone
glycoprotein hormones - luteinising, TSH - glycosylated
lipid and phospholipid hormone
eicosanoids (prostaglandin etc) - in immune system and BV regulation and clotting
steroids - derived from cholesterol
calcitriol (vit.D) - sterol derived hormone, no metabolic pathway - cant produce from scratch
solubility amine-derived and peptide hormones
water soluble - go to receptor will sit at specific phase
hormone-receptor interaction
H released from CPr and bind to receptor = hormone receptor complex
interaction
defined by Kd 1:1 reaction stronger v. specific and Kd reange from 10(-9) to 10(-12) molar reversible
interaction - 1:1 reaction
[H][R] / [HR]
interaction - stronger
more in HR state - smaller ratio
free:bound
HR
hormone-receptor
interaction - reversible
measure of affinity - ease of separation Kd
Kd
[H]
half of all R are bound - [R] = [HR]
max biological response
B max
most have hormone efficiency far lower than what is seen when all R or bound
Kd at 50% level
example of max response - insulin
bind on adipocytes = uptake metabolites - occur at max level at 2-3% receptor bound
amplification downstream signalling system
[H] need for max response
sensitivity of system
limiting step in hormonal system - H bind to R - amplification - efficient
driven by secondary messenger/ downstream phosphorylation cascade
[H] seen by target cell depend on
rate of release
rate of delivery
rate of degradation and elimination
rate of release
depend on synthesis and selection of H
highly regulated of endocrine control by +ve and -ve feedback loop
rate of delivery
blood flow to organ(faster) - increase chance of HR complex
carriers - bring H - stop being broken down
rate of degradation and eliminating
H-characteristic rate of decay-metabolised and excreted
e. g. adrenaline - shutting off secretion H with short half life - decrease rapidly
e. g. thyroid hormone - H’s long biological half life - effective conc persist
ways to measure levels of H
radioimmune assay
elisa
radioimmune assay - process
need Ab against H and isolate H radiolabelled = complex and precipitate out radioactive H
complex with sample of unlabelled H down with it
compare known and unknown conc = amount of H/ molecule - present
Ab
antibodies
Elisa - needs 2 antibodies - process
plastic surface - capture Ab and H and second Ab bind at another site = amplification system
enzyme links to first detected Ab against detecting Ab
which build pyramid - enzyme attach = S. oxidised and change colour
endocrine system - where receptor are sitting on cell - types
hydrophilic
hydrophobic
hydrophilic receptors in endocrine system
ion channel linked
enzyme and G protein linked (need carrier) which have second messenger
hydrophobic receptor in endocrine system
plus example
cytoplasmic - no second messenger
able to move through membrane and bind to R
= turn off effect/ be carried to R to target area
e.g. thyroid - gets carried into nucleus - drives mRNA expression
where hormones are secreted from - 2 type
primary endocrine organ
secondary endocrine organ
both secrete H
primary endocrine organ example
pancreas, parathyroid H, Pit. etc
secondary endocrine organ + example
secrete H as secondary function
e.g. heart, stomach, liver, kidney, small intestine, skin, ovaries and testes etc
pheromone
ectohormone - signalling molecules released into environment
adipocytes
endocrine hormone
make lectin
bone - as endocrine organ have examples
e.g. thymus, muscle etc
endocrine(ductless) gland derive from epithelia
adrenal cortex and beta cells
endocrine(ductless) gland derive from neurons
neurohormones
endocrine(ductless) gland derive from isolated cells
diffuse endocrine cells- intestines
gut, heart etc
immune cell - cytokine function
active at low conc and carried in blood
controlling endocrine system - simple feedback loop e.g. “A”
"A" changes conc gland responds to conc hormone released bind to target cells - respond by releasing/absorbing A repeat
examples of the simple feed back loop
intestinal H, secretin, Gastrin, CCK insulin, Glucagon-paired
beta cells monitor glucose levels - feedback loop
glucagon (alpha cell) - increase blood sugar - breakdown glucagon
insulin (beta cell) - decrease blood sugar - absorb glucose
regulating extracellular [Ca2+] - 2 hormones used
calcitonin - produced by C cells - between follicles in thyroids parathyroid H (pH) by parathyroid - surface of thyroid
regulating extracellular [Ca2+] process when decrease in [Ca2+]
parathyroid become excited - release pH into blood
pH bind on osteocyte and osteoclast - break down bone
regulating extracellular [Ca2+] process (1) in late distal tubule
matrix = Ca2+ - bind on kidney tubule - increase uptake of Ca
activated=s kidney - 1,2-DiOH cholecalciferol = decrease Ca secretion and increase its absorption
change in [Ca2+] monitored by
C cells - release calcitonin - decrease [Ca2+]
hyperparathyroidism - disease
too much
primary - more bone breakdown = demineralised
calcification and stone formation
secondary - renal failure - decrease in Ca2+ by kidney - increase parathyroid activity
hypoparathyroidism - disease
too little
autoimmune
Ab made against parathyroid gland
increase action potential in tissue and heart
decreases inhibition of voltage gated Ca2+ channel
