Endocrinology 2- Hormone Bioavailability Flashcards
How can hormone transport affect bioavailability
How much is bound vs unbound (binding proteins), kinetics (half life and metabolism)
How can target tissues affect hormone bioavailability
Receptors (if there are any mutations, desensitization, half life issues, up or down regulation of the receptors); as well as chaperone and heat shock proteins that may be associated with the receptor
How can hormone synthesis and release affect hormone bioavailability
Enzymatic activity; processing and packaging
How regulatory mechanisms can affect hormone bioavailability
Feedback mechanisms, circadian rhythms, aging, pulsitility
What is some information the classification of a hormone’s chemical makeup can tell you?
How the hormone is synthesized and released from the cell, how long a hormone is in circulation, how it travels in circulation (bound/unbound), the receptor type that will mediate the action, cellular signaling pathways
Usual half life of an amine hormone
2-3 minutes
Two types of amine hormones (chemically speaking)
Catecholamines, indoleamines
What are Catecholamines (chemically speaking, what are they derived from)
Tyrosine
What are indoleamines derived from chemically speaking
Tryptophan
What is the general half life of a peptide or protein hormone
Can vary - on avg 4-170 minutes
General half life of a steroid hormone
Minutes to several hours
Very helpful, thank you
Tyrosine derived Catecholamines hormones include what 3 main players
Dopamine, epinephrine, norepinephrine
What is the rate limiting step in Catecholamine biogenesis
Tyrosine hydroxylase
What 2 main body organs houses dopamine
Brain (substantia migraine, VTA, accurate nucleus), and adrenal gland
In brain, what is the “endocrine” generator of dopamine
Arcuate nucleus
What is the enzyme that catalyzes the reaction to generate norepinephrine
Dopamine b-hydroxylase
Where is most norepinephrine generated
Neurons
What is the nerve from SNS that innervates adrenal medulla to get NE/E?
Splanchnic nerve
What are the cells in the adrenal medulla that make Epinephrine
Chromaffin cells (in adrenal medulla)
What are the major 2 indoleamines in the body
Serotonin and melatonin
What is the rate limiting enzyme in indoleamine synthesis
Tryptophan hydroxylase
What is the first step in indoleamine synthesis
AADC (aromatic L amino acid decarboxylase)
Where is the majority of serotonin produced
Gut (enterochromaffin cells)
What converts serotonin to melatonin (rate limiting step)
N-acetyltransferase
What is special about n-acetyltransferase
It is only active at night
How do we break down amine hormones? Two pathways
MAO (monoamine oxidase) and COMT (Catecholamines-o-methyltransferase)
MAO
Monoamine oxidase - removes an amine group, oxidative delaminating - get aldehyde instead of amine. Inactivates both Catecholamines and indoleamines
MAOI
MAOI’s are pharmaceutical drugs used to treat depression and anxiety disorders
COMT
Adds methyl group to allow substance to be metabolized, specific to catecholamine. This is inhibited by entacapone which is a Parkinson’s drug, to try to increase levels of dopamine.
Monoamine deaminating steps
1 - deamination, form aldehydes
2- aldehydes are converted to alcohol or metabolizes by aldehyde dehydrogenase or aldose reductase
3. DHPG is the primary metabolite in sympathetic nerves - major pathway for catecholamine metabolism
COMT methylation - steps
Major source of metanephrine and normetanephrine in adrenal gland - converts DHPG to MHPG which is a precursor of VMA — this is excreted into urine — if you have high Catecholamines especially. This is a good diagnostic tool to look for tumors
How are protein/peptide hormones first generated?
Preprohormone
What does a preprohormone consist of?
Signal peptide + hormone + additional copeptides
Where is the signal peptide cleaved
In the ER
Where are copeptides cleaved from prohormone
This is going to be cleaved in Golgi/sometimes within vesicles themselves
Where are steroid hormones made
Placenta, adrenal gland, testes, ovaries
21 carbon steroids include what 3 hormones
Glucocorticoids, mineralocorticoids, and progestins
19-carbon steroids include what hormones
Androgens
18-carbon steroid hormones includes
Estrogens
What is our body’s main secosteroid
Vitamin d
For dick
Precursor to all of our steroid hormones
Pregnenolone
What are the few instances we will see positive feedback
Parturition (childbirth) and lactation (suckling) — both of these include oxytocin
Ovulation — LH stimulates estradiol in developing follicle, estradiol stimulates more LH, then release of OOcyte eventually stops loop
What is an endocrine axis?
A three tiered biological system made of hypothalamic neurons, anterior pituitary cells, and peripheral endocrine gland
What is a long feedback loop
Feedback of the molecule feeding back at pituitary or hypothalamic level
What is a short feedback loop
Molecule from pituitary goes back and feeds to hypothalamus to tell it to fucking stop
2 major types of negative feedback
Physiological response drive
Endocrine axis driven
Physiological response driven negative feedback
Endocrine gland releases hormone, hormone does its thing to target organ, physiology is changed, for example blood glucose, gland detects change in physiology and stops releasing as much hormone
Endocrine axis driven negative feedback
Peripheral organ releases a hormone and directly says “stop” to pituitary or hypothalamus, or pituitary feeds back to hypothalamus (long/short loops respectively) and this is what stops the cycle
What are some factors that affect circulating hormone levels
Age, body weight, time of day, male/female, diet
