Lecture 2 Flashcards
What are the 3 molecular classes of hormones?
1) amines
2) peptide/proteins
3) steroids
What are some examples of hormones in the amine category?
catecholamines
indoleamines
thyroid hormone
Catecholamines are derived from a single __________
tyrosine
Indolamines are derived from a single ___________
trypotophan
Thyroid hormone is derived from ____ _____________
2 tyrosines
What type of hormones have the shortest half life?
amines (2-3 minutes)
What is the half life of T4?
8 days
What is the half life of T3?
24 hours
What is the half life of proteins?
4-170 minutes
What is the half life of steroids?
minutes to several hours
Are catecholamines/indoleamines bound or free in the blood?
FREE (travel very quickly and are used rapidly)
How do catecholamines/indoleamines enact their signaling?
bind to membrane receptor to activate second messenger signaling
How do catecholamines/indoleamines enact their signaling?
bind to membrane receptor to activate second messenger signaling ALWAYS
What is the main difference between catecholamines and indoleamines?
SYNTHESIS
tyrosine - cat
tryptophan - indol
What are 3 catecholamines?
1) Dopamine
2) Norepinephrine
3) Epinephrine
What is the rate limiting step in catecholamine synthesis?
Tyrosine hydroxylase (used as a marker for dopaminergic activity)
catalyzes reaction of tyrosine to L-DOPA
Where does conversion of DOPA occur?
adrenal medulla
What is dopamine converted into?
NE and E (adrenaline)
What is the main endocrine function of dopamine?
INHIBIT prolactin release from the anterior pituitary
Dopamine neurons arise from the _________ _________ in the hypothalamus
arcuate nucleus
What are the 3 places in the brain where dopamine is made?
1) Substantia nigra
2) ventral tegmental area
3) arcuate nucleus of hypothalamus
In addition to the brain, where else is dopamine made?
adrenal medulla (where it is converted to NE)
True or false: dopaminergic neurons of the arcuate nucleus are always firing to tonically inhibit prolactin?
TRUE
always being released because tyrosine hydroxylase is tonically active
What enzyme catalyzes the conversion of dopamine to NE?
dopamine beta-hydroxylase
What leg of the ANS stimulates dopamine beta hydroxylase?
sympathetics
What type of neuron releases NE?
sympathetic post ganglionic
What innervates the adrenal medulla where conversion to NE occurs?
splanchnic nerves
Does NE act via alpha or beta adrenergic receptors?
BOTH
What cells the of the adrenal medulla release NE?
chromaffin cells (homologous to postsynaptic sympathetic neurons)
What cells the of the adrenal medulla release NE?
chromaffin cells (homologous to postsynaptic sympathetic neurons)
What is the rate limiting enzyme of indoleamine synthesis?
Tryptophan hydroxylase
What is an example of an indoleamine?
serotonin
Where is serotonin made?
95% in the gut
5% raphe’s nucleus
What does serotonin do?
act as a vasoconstrictor, stimulates smooth muscle contraction in intestine
Where is serotonin made?
95% in the gut (ECCs)
5% raphe’s nucleus
What does serotonin do?
act as a vasoconstrictor, stimulates smooth muscle contraction in intestine
What is the molecular formula for tryptophan to melotonin?
tryptophan ——> serotonin —–> melotonin
What is the rate limiting enzyme for serotonin to melatonin conversion?
N-acetyltransferase (SNA)
Where is melatonin produced?
pineal gland
What is the neurotransmitter in the brain that is referred to as the “happiness hormone”
Serotonin
What is the molecular basis of SSRIs? (selective serotonin reuptake inhibitors)
increase concentration of serotonin at the synaptic cleft by BLOCKING reuptake so serotinin can sit in the cleft longer
What is a complication with the logic of SSRIs?
lots of serotonin downregulates receptors so you cannot see effect of SSRIS - nothing to respond to increased amount of neurotransmitter in the cleft
What enzyme catalyzes conversion of L-DOPA to dopamine?
Dopa decarboxylase
What is the clinical importance of monoamine oxidase inhibitors? (MAO inhibitors)
catalyzes deamination of monoamines, increases dopamine (used in depression)
What 2 classes of drugs enact monoamine inactivation?
1) DDC inhibitors (increase L-Dopa conc): Carbidopa and Benzerazide
2) COMT inhibitor (prevents inactivation and degradation of catecholamines): Entacpone
3) MAO inhibitors
What is MAO and what does it do?
monoamine oxidase - catalyzes oxidative deamination of all monoamines
What MAOs are present in humans?
MAOA and MAOB
What effect does Entacapone have on dopamine
inhibits COMT (inhibits deactivation outside of cell)
What effect does Carbidopa and Benzerazide have on dopamine?
inhibits conversion outside cell
When is N-acetyltransferase active in the converting serotonin to melatonin?
during the night
How does melatonin affect reproduction?
inhibits it! decreased spermatogenesis and testis size
How is melatonin secretion regulated?
light info is conveyed to the SCN via the retinohypothalamic tract (RHT) which then the SCN transmits that info to the pineal gland
Peptide hormones are transcribed as ______________
preprohormones
Peptide hormones are transcribed as ______________
preprohormones
Once the signal peptide is cleaved, a prohormone is formed which includes _________ and _______
hormone and copeptides
Once the signal peptide is cleaved, a prohormone is formed which includes _________ and _______
hormone and copeptides
What has a longer half life, hypothalamic or pituitary hormones?
Pituitary
What hormone has the longest half life?
IGF-1
Steroids are all derived from __________ precursor
cholesterol
What is the central precursor which forms all steroid hormones?
Pregnenolone (forms aldosterone, cortisol, estrogens/androgens)
What is responsible for carriage of cholesterol from the outer mitochondria to the inner?
StAR
What is the main endocrine axis?
HPA (hypothalamic - pituitary)
hormones can regulate any part of axis)
Short loop feedback is from _______ to _______
pituitary to hypothalamus
Long loop feedback is from __________ to __________
endocrine to hypothalamus
Long loop feedback is from __________ to __________
endocrine to hypothalamus
What are the 4 examples of positive feedback systems in the human body?
1) Partuition (more contractions, more oxytocin until birth stops)
2) Lactation (more suckling, more oxytocin until baby stops feeding)
3) Ovulation (LH stimulates estradiol which stimulates more LH until oocyte is released)
4) Blood clotting (tissue injury activates platelets which activate more platelets until clotting stops)
What is the only NON-reproductive positive feedback?
blood clotting
What is the only NON-reproductive positive feedback?
blood clotting
What is the HPA flow for T3/T4 hormones?
TRH (hypo) –> TSH (ant. pit.) –> T4/T3
What is a primary thyroid problem?
problem with T4/T3 secretion
Where is a secondary thyroid problem?
pituitary (TSH secretion)
Where is the problem in a tertiary thyroid problem?
hypothalamus
How would you diagnose a secondary thyroid problem?
Undetectable TSH and unresponsive to TRH
What is euthyroid sick syndrome?
normal TSH and thyroid but low T4/T3 (hypothyroid symptoms)
What hormone is looked at to assess heart failure?
BNP
Which heart hormone has a longer half life?
BNP
What do ANP and BNP do?
promote water shedding - opposite effect of AVP and aldosterone
What do ANP and BNP do?
promote water shedding - opposite effect of AVP and aldosterone
Do women or men have higher ANP and BNP?
women (increases with age)
