Endocrine 2: basics Flashcards
What are the chemical categories of hormones?
- monoamines (catecholamines and indolamines)
- peptides/proteins
- steroids
Characterize monoamines.
- short half life
- transported freely in the blood
- bind to surface membrane receptor and activate second messenger signaling cascade
What is the most common chemical composition of hormones?
- peptides/proteins
List hormone categories in order of their half-life (short to long).
- monoamines
- peptides/proteins
- steroids
What is the main difference between catecholamines and indolamines?
- catecholamines are derived from tyrosine via tyrosine hydroxylase
- indolamines are derived from tryptophan via tryptophan hydroxylase
Describe the enzymatic reaction that forms catecholamines.
tyrosine => tyrosine hydroxylase => L-DOPA => dopamine => norepi/epi
What is the rate limiting step for all catecholamine formation?
tyrosine hydroxylase
- used as biomarker of dopaminergic activity
What is unique about catecholamines?
act as hormone and neurotransmitter
Where is dopamine produced?
Brain
- arcuate nucleus (tonically express TH; unaffected by Parkinson’s; released to anterior pituitary)
- substantia nigra/ventral tegmental area (affected by Parkinson’s)
Adrenal Medulla
- converted to norepi/epi via dopamine beta-hydroxylase
What is the function of dopamine?
- arcuate nucleus => hypophysial capillary bed (bloodstream) => pituitary gland => inhibits prolactin release
- reward centers, mood in the brain
- conversion to norepi/epi
What are the functions of norepinephrine?
- function as neurotransmitter and hormone
- requires sympathetic stimulation
- conversion from dopamine takes place in neurons
- dopamine => dopamine beta-hydroxylase => norepinephrine
Describe the 2 mechanisms of sympathetic norepinephrine release.
- preganglionic neuron => ACh on nicotinic receptors => postganglionic neuron => norepi on alpha and beta adrenergic receptors
- preganglionic neuron (splanchnic) => ACh on chromaffin cells in adrenal medulla => make dopamine => converted to norepi/epi => epi mainly released
List catecholamines.
dopamine
norepinephrine
epinephrine
List indolamines.
serotonin
melatonin
Characterize indolamines.
- rate limiting step is tryptophan hydroxylase
- serotonin is both neurotransmitter and hormone
- melatonin is a hormone produced by pineal gland
Describe serotonin.
- both neurotransmitter and hormone
- aka 5-hydroxytryptamine (5-HT)
- majority is produced in the gut
- acts as vasoconstrictor and smooth muscle contractions in the gut
- happiness hormone
Describe the use of SSRIs.
- Selective Serotonin Reuptake Inhibitors
- block reuptake proteins on the terminal end of releasing neurons
- causes increase of serotonin remaining in the synaptic cleft to increase duration of action
- used to treat mental health disorders
What are some clinical considerations of SSRIs?
- receiving neuron will downregulate serotonin receptors
- negative feedback will cause releasing neuron to downregulate serotonin production
- not effective in most patients
How is melatonin produced?
serotonin => N-acetyltransferase (SNA) => melatonin
- SNA is rate limiting enzyme
- most actively produced at night
- made in pineal gland
How is melatonin used clinically? What are some clinical considerations?
- used to treat insomnia, jet lag, SAD, migraines
- inhibits reproduction => decreased testosterone and testis size in males
Describe how melatonin secretion is regulated.
Requires prolonged hours of darkness to reach maximum activity
- light => retinohypothalamic tract => SCN => pineal gland => regulates circadian rhythms
Describe protein hormone processing.
- after transcription/etc = preprohormone = signal (to ER), hormone, and copeptide
- after translation = signal diverts it to the ER => signal degraded
- prohormone = hormone + copeptide
- cleavage and packaging => hormone = active form; copeptide can have other effects
What is the relationship between peptide composition and half life? What is the exception?
In general, the shorter the peptide hormone, the shorter the half-life
- IGF1 has a long half-life because it is bound to protein in plasma
List the steroid hormones made in the following organs:
- adrenal cortex
- kidney
- placenta
- testis
- ovary
- adrenal cortex = cortisol, mineralcorticoids, DHEA, androstenedione
- kidney = vitamin D
- placenta = progesterone, estriol
- testis = testosterone
- ovary = 17D-estradiol, progesterone
Describe cholesterol derivative synthesis in the adrenal gland.
- cholesterol enters the inner mitochondria via StAR protein, which also houses P450scc, an enzyme that converts cholesterol to pregnenolone
- defects in StAR/P450scc is embryonic lethal
What is an endocrine axis?
3-tier
- hypothalamus
- pituitary
- peripheral organ
Describe endocrine axis negative feedback.
- short loop = pituitary hormone will negatively feedback on to the hypothalamus
- long loop = peripheral endocrine hormone will negatively feedback on the pituitary and/or hypothalamus
Describe physiological driven negative feedback.
There is no hormone released by the target organ. Instead, there is a change in the physiological state that immediately causes cessation of hormone production.
List examples of positive feedback.
- oxytocin during childbirth
- oxytocin during suckling
- LH => estradiol in developing follicle => more LH => oocyte released
- blood clotting via platelets at site of tissue injury
List factors that affect “normal” circulating hormone levels.
- sex
- age
- time of day
- weight
- diet
How do certain hormones change with age?
- catecholamines and glucocorticoids increase with age
- testosterone increases during puberty and decreases with age
- estrogen sharply increases during puberty and sharply declines during menopause
- androgens peak at mid-20s and then decrease with age
Describe “normal” circulating ANP/BNP and the factors that contribute to it.
Sex - men range = 4-40 - women range = 8-80 (doubled) Weight - decreased in obese pts Age - increases with age
- used to rule out congestive heart failure (BNP - b/c longer half-life)
- elevated in heart and renal failure
Describe monoamine metabolism.
MonoAmine Oxidase (MAO) - oxidative deamination removes an amine group => aldehyde and ammonia => Aldehyde Dehydrogenase (AD) => further metabolizes aldehyde - inactivates both catecholamines and indolamines
Catechol-O-MethylTransferase (COMT) - adds methyl group to catecholamines only
What is the clinical use of monoamine metabolism?
- MAOIs inhibit catecholamine metabolism => longer duration of action (used in depression to increase activity of dopamine)
Define DHPG.
- primary metabolite of catecholamines found in extraneural tissue
Define VMA.
VanillylMandelic Acid
- urinary indicator of excessive catecholamine production
- used to diagnose catecholamine producing tumors
- end metabolite of catecholamine metabolism
