Endocrine 2: basics Flashcards

1
Q

What are the chemical categories of hormones?

A
  • monoamines (catecholamines and indolamines)
  • peptides/proteins
  • steroids
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2
Q

Characterize monoamines.

A
  • short half life
  • transported freely in the blood
  • bind to surface membrane receptor and activate second messenger signaling cascade
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3
Q

What is the most common chemical composition of hormones?

A
  • peptides/proteins
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4
Q

List hormone categories in order of their half-life (short to long).

A
  • monoamines
  • peptides/proteins
  • steroids
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5
Q

What is the main difference between catecholamines and indolamines?

A
  • catecholamines are derived from tyrosine via tyrosine hydroxylase
  • indolamines are derived from tryptophan via tryptophan hydroxylase
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6
Q

Describe the enzymatic reaction that forms catecholamines.

A

tyrosine => tyrosine hydroxylase => L-DOPA => dopamine => norepi/epi

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7
Q

What is the rate limiting step for all catecholamine formation?

A

tyrosine hydroxylase

- used as biomarker of dopaminergic activity

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8
Q

What is unique about catecholamines?

A

act as hormone and neurotransmitter

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9
Q

Where is dopamine produced?

A

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

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10
Q

What is the function of dopamine?

A
  • arcuate nucleus => hypophysial capillary bed (bloodstream) => pituitary gland => inhibits prolactin release
  • reward centers, mood in the brain
  • conversion to norepi/epi
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11
Q

What are the functions of norepinephrine?

A
  • function as neurotransmitter and hormone
  • requires sympathetic stimulation
  • conversion from dopamine takes place in neurons
  • dopamine => dopamine beta-hydroxylase => norepinephrine
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12
Q

Describe the 2 mechanisms of sympathetic norepinephrine release.

A
  1. preganglionic neuron => ACh on nicotinic receptors => postganglionic neuron => norepi on alpha and beta adrenergic receptors
  2. preganglionic neuron (splanchnic) => ACh on chromaffin cells in adrenal medulla => make dopamine => converted to norepi/epi => epi mainly released
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13
Q

List catecholamines.

A

dopamine
norepinephrine
epinephrine

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14
Q

List indolamines.

A

serotonin

melatonin

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15
Q

Characterize indolamines.

A
  • rate limiting step is tryptophan hydroxylase
  • serotonin is both neurotransmitter and hormone
  • melatonin is a hormone produced by pineal gland
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16
Q

Describe serotonin.

A
  • 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
17
Q

Describe the use of SSRIs.

A
  • 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
18
Q

What are some clinical considerations of SSRIs?

A
  • receiving neuron will downregulate serotonin receptors
  • negative feedback will cause releasing neuron to downregulate serotonin production
  • not effective in most patients
19
Q

How is melatonin produced?

A

serotonin => N-acetyltransferase (SNA) => melatonin

  • SNA is rate limiting enzyme
  • most actively produced at night
  • made in pineal gland
20
Q

How is melatonin used clinically? What are some clinical considerations?

A
  • used to treat insomnia, jet lag, SAD, migraines

- inhibits reproduction => decreased testosterone and testis size in males

21
Q

Describe how melatonin secretion is regulated.

A

Requires prolonged hours of darkness to reach maximum activity
- light => retinohypothalamic tract => SCN => pineal gland => regulates circadian rhythms

22
Q

Describe protein hormone processing.

A
  1. after transcription/etc = preprohormone = signal (to ER), hormone, and copeptide
  2. after translation = signal diverts it to the ER => signal degraded
  3. prohormone = hormone + copeptide
  4. cleavage and packaging => hormone = active form; copeptide can have other effects
23
Q

What is the relationship between peptide composition and half life? What is the exception?

A

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

24
Q

List the steroid hormones made in the following organs:

  • adrenal cortex
  • kidney
  • placenta
  • testis
  • ovary
A
  • adrenal cortex = cortisol, mineralcorticoids, DHEA, androstenedione
  • kidney = vitamin D
  • placenta = progesterone, estriol
  • testis = testosterone
  • ovary = 17D-estradiol, progesterone
25
Describe cholesterol derivative synthesis in the adrenal gland.
1. cholesterol enters the inner mitochondria via StAR protein, which also houses P450scc, an enzyme that converts cholesterol to pregnenolone 2. defects in StAR/P450scc is embryonic lethal
26
What is an endocrine axis?
3-tier 1. hypothalamus 2. pituitary 3. peripheral organ
27
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
28
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.
29
List examples of positive feedback.
1. oxytocin during childbirth 2. oxytocin during suckling 3. LH => estradiol in developing follicle => more LH => oocyte released 4. blood clotting via platelets at site of tissue injury
30
List factors that affect "normal" circulating hormone levels.
- sex - age - time of day - weight - diet
31
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
32
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
33
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
34
What is the clinical use of monoamine metabolism?
- MAOIs inhibit catecholamine metabolism => longer duration of action (used in depression to increase activity of dopamine)
35
Define DHPG.
- primary metabolite of catecholamines found in extraneural tissue
36
Define VMA.
VanillylMandelic Acid - urinary indicator of excessive catecholamine production - used to diagnose catecholamine producing tumors - end metabolite of catecholamine metabolism