Basics of Endocrinology II Flashcards
What are amine hormones derived from and what is their half life?
a single amino acid, 2-3 minutes
What are catecholamines derived from
A single tyrosine
What are indolamines derived from?
A single tryptophan
What is T4/T3 derived from and what are their half lives?
Two tyrosines - the exception to amines
Half life T4 = 8 days, T3 = 24 hours
What chemical classification are most hormones?
peptides/proteins
What is the half life of peptide/protein hormones?
4-170 minutes
What is the half life of steroid hormones?
minutes to several hours - generally the longest half life of the hormones (exception, thyroid hormones)
What are the three chemical classifications of hormones?
amines, peptide/proteins, steroid
What are the common features of catecholamines and indolamines?
short half life - act quickly and are degraded quickly
travel freely in the blood
always activate a membrane receptor to activate a signaling cascade
What is the major difference between catecholamines and indolamines?
synthesis
Catecholamines synthesized from tyrosine via tyrosine hydroxylase (rate limiting)
Indolamines synthesized from tryptophan via ryptophan hydroxylase (rate limiting)
What are some tyrosine derived catecholamines?
Dopamine, Norepi, Epi
How can tyrosine hydroxylase be used clinically?
It can be used as a marker of dopaminergic activity
What are the two ways in which dopamine can act?
NT and a hormone
What organs is dopamine made in?
Brain: Substantia nigra, ventral tegmental area, arcuate nucleus (for release to pituitary)
Adrenal glands: the adrenal medulla is where it is converted into norepinephrine
What is the function of dopamine in the brain?
Regulates many pathways as a NT, involved in reward pathways, attention, and mood
What is the hormone action of dopamine?
Inhibits prolactin release from the anterior pituitary (tonic inhibitor)
In the control of prolactin release, where do the dopaminergic neurons arise from, and where do they synapse?
Arise from the arcuate nucleus, synapse on the hypophyseal capillary bed
What are the two ways in which norepinephrine can act?
NT, hormone
From what is norepi derived from?
dopamine (which is derived from tyrosine)
What is required to convert dopamine to norepi?
sympathetic stimulation
What is the rate limiting enzyme in the conversion of dopamine to norepi?
dopamine-beta-hydroxylase
Where does the conversion of dopamine to norepi happen, and how do we know?
The tissue concentrations are equivalent to that of the synapse - thus the conversion must take place within the neurons
What do sympathetic post-ganglionic fibers release?
NE!
Through what kind of receptors does NE act through?
alpha and beta adrenergic receptors
How is the adrenal medulla involved in NE release?
splanchic nerve innervates the adrenal medulla where conversion to NE occurs
Chromaffin cells of the adrenal medulla are homologous to post-ganglionic fibers and will release NE into the blood
What is the rate limiting enzyme of indoleamine synthesis?
tryptophane hydroxylase
What is an example of an indoleamine that is both a hormone and a NT?
Serotonin
What can be formed from serotonin?
Melatonin
What is the enzyme in the synthesis of melatonin from serotonin?
SNA
Where is melatonin produced?
Pineal gland
What is serotonins action as a NT, and where is it located?
the brain, is the ‘happiness hormone’
Where is the majority of serotonin produced, and by what cells?
over 95% of serotonin is produced by enterochromffin cells of the gut
What is serotonins activity in the gut?
vasoconstrictor
stimulates smooth muscle contraction in intestine
How do SSRIs work?
Block the reuptake of serotonin (inhibit 5-HT) thus increasing serotonin concentrations in the synaptic cleft
What can happen with long term SSRI use?
down-regulation of serotonin receptors or the neuron can stop making endogenous serotonin if used for prolonged periods
What are the two primary methods of mono-amine metabolism and what are the enzymes involved?
deamination and methylation
MAO: oxidative deamination - inactivates indoleamines and catecholamines via removal of an amine group resulting in aldehyde and ammonia (aldehyde degraded via aldehyde dehydrogenase)
COMT: metabolism of catechoamines - adds a methyl group
What do MAOIs do?
inhibit MAOand thus are used for depression and anxiety disorders
What is the primary metabolite of catecholamines in extraneural tissues?
DHPG
What is a metabolite in urine that can indicate excessive catecholamines?
Vanillylmandelic acid (VMA)
from what is melatonin synthesized, and where?
from serotonin in the pineal gland
What is the rate limiting enzyme in melatonin synthesis, and when is it most active?
N-acetyltransferase, at night
What does melatonin inhibit?
It is a potent inhibitor of reproduction - it causes decreased spermatogenesis and testis size in males
Discuss the events required for melatonin secretion
light info transmitted to the SCN via the retinohypothalamic tract
the SCN transmits the info to the pineal gland and regulates its circadian activity
Describe the path of a gene to a protein hormone
DNA - mRNA - translated to a preprohormone - NH2 signal is cleaved to give a prohormone - additional peptides cleaved to give hormone
What are all steroids derived from?
Cholesterol
What are the steroid hormones of the adrenal cortex?
Cortisol, mineralocorticoid, DHEA, androstenedione
What is the steroid hormone of the kidney?
Vit. D
What are the steroid hormones of the placenta?
progesterone, estriol
What is the steroid hormone of the testis?
testosterone
What are the steroid hormones of the ovaries?
17beta-estradiol, progesterone
What is a common precursor of steroid hormones, and how is it formed?
StAR moves cholesterol from the outer to the inner mitochondrial membrane and forms pregnenolone
What are the different fates of pregnenolone?
Cortisol via several hydroxylation steps
Estrogens and androgens via DHEA and the enzyme 3betaHSD
progesterone via 3betaHSD and subsequent metabolism to aldosterone via hydroxylation rxns and the enzyme aldosterone synthase
What is an endocrine axis?
Three-tiered endocrine system involving hypothalamic neurons, anterior pituitary cells, and peripheral endocrine glands
hormones can regulate any part of this sequence
What is short and long loop negative feedback?
short loop: hormone from pituitary acts on hypothalamus
long loop: hormone released from peripheral gland can act on both the pituitary and the hypothalamus
What is the difference between endocrine axis driven- and physiological response driven- negative feedback?
physiological response driven (used to be called feed forward) - the physiological effect of the hormone is what results in a change, not the hormone itself as in endocrine axis driven
What are four examples of positive feedback?
parturition
lactation
ovulation
blood clotting
What factors affect circulating hormone levels?
Age, sex, time of day, body weight, diet
