72 - Basics continued Flashcards
(78 cards)
1
Q
How long is half-life of amine hormones?
Peptide/protein hormones?
Steroid hormones?
A
- Monoamines: 1-3 min
- Peptide/ptn: 4-170 min
- Steroid: min - several hrs
2
Q
What are the 2 classes of monoamines?
A
- Catecholamines
- Indoleamines
3
Q
How do monamines travel in the blood?
A
Freely
4
Q
Describe the pathway of formation of catecholamines (don’t give enzymes).
A
Tyrosine -> XDOPA -> Dopamine -> NE -> epi
5
Q
Can catecholamines act as a hormone, NT, or both?
A
Both
6
Q
What hormone is the exception to the monoamines?
A
TH (we will see)
7
Q
What is the RLS of catecholamine catabolism?
A
Tyrosime -> XDOPA (*tyrosine hydroxylase)
- Tyrosine hydroxylase often used as a marker for dopaminergic activity
8
Q
How long is the half-life of monoamines?
A
Very short (1-2, 3 minutes)
9
Q
What enzyme converts NE to epi?
A
Phenylethanolamine-N-methyltransferase (PNMT)
10
Q
In what 3 major brain areas is dopamine synthesized?
A
- VTA
- SN
- Arcuate nucleus
(reward pw’s, attn, food)
11
Q
Besides the brain, what other gland makes dopamine?
What is it converted to there?
A
Adrenal gland
- Converted to NE
12
Q
What is dopamine’s specific endocrine action?
it’s a NT as well as a hormone
A
Tonic inhibitor of PRL in ant. pit.
13
Q
Dopaminergic neurons arise from the __________ of the hypothalamus.
A
Arcuate nucleus
14
Q
Where does dopamine (directly) go upon its release from the arcuate nuc of the hypo?
A
Into the hypophyseal capillary bed
15
Q
Does NE function as a NT, hormone, or both?
A
Both
16
Q
What does NE require for its release?
A
Symp NS stimulation
17
Q
What general type of cell convert most of the dopamine into NE?
A
Neuron
18
Q
What enzyme converts dopamine to NE?
A
Dopamine beta-hydroxylase
19
Q
What class of neurons release NE?
A
Sympathetic post-ganglionic neurons
20
Q
What specific types of receptors does NE act on? (released from sympathetic post-ganglionic neurons)
A
Alpha and beta-andrenergic receptors
21
Q
Where is NE converted to epi?
What nerve innervates this?
A
Adrenal medulla
- Splanchnic n.
22
Q
What is the names of the types of cells that release NE/epi into the blood in the adrenal medulla?
A
Chromaffin cells (analogous to post-sympathetic neurons)
23
Q
While post-ganglionic sympathetic cells secrete NE, pre-ganglionic cells secrete _________/
A
ACh
24
Q
Recall: what substrate do catecholamines derive from?
A
Tyrosine
25
What substrate do indoleamines derive from?
Tryptophan
26
Describe the pathway of formation of indoleamines (don't give enzymes).
Tryptophan -> Serotonin -> (intermediate) -> melatonin
27
What is the RLS of indoleamine catabolism?
Tryptophan hydroxylase (TPH)
28
What hormone is known as the "happiness hormone"?
| Is it also a NT?
Serotonin (5-HT)
| - Yes
29
95% of 5-HT is made in the ___________ via ___________ cells.
- Gut
| - Enterochromaffin
30
What are 5-HT's actions in the gut?
- Vasoconstriction of smooth mm.
| - Smooth m. cell contractions in intestine
31
How do SSRIs work?
| What are 2 possible issues w/them?
Block 5-HT reuptake, supposedly leaving them in synaptic cleft to work longer
- Desensitization/down-regulation of receptors
- Negative feedback--less 5-HT produced in pre-synaptic cells
32
Name the 2 primary mechs of monoamine metabolism.
- Deamination
| - Methylation
33
Name the 2 major enzymes that function in monoamine inactivation.
What's a 3rd enzyme that works on dopamine?
- Monoamine oxidase (MAO)
- Catechol-O-methyltransferase (COMT)\
- Dopa decarboxylase (DDC)
34
What does dopa decarboxylase do?
| Why would you use this for treatment?
Converts dopamine -> L-DOPA
| - L-DOPA can cross BBB (dopamine can't), therefore use to treat PD, etc.
35
Does COMT inactivate catecholamines, indoleamines, or both?
Catecholamines only
36
Does MAO inactivate indoleamines, indoleamines, or both?
Both
37
How could MAO-inhibitors be used to treat depression and other mood disorders?
Increase dopamine (stops it's breakdown, along with NE and epi)
38
In catecholamine metabolism, what is DHPG?
What is required to metabolize it?
What's it broken down into?
Primary metabolite in extraneural tissues (last step; occurs in liver, kidneys)
- COMT and aldehyde DH
- VMA (vanilylmandelic acid)
39
What is VMA, or vanilylmandelic acid, an indicator of?
Urinary indicator of catecholamines
| might be elevated w/certain tumors
40
Prior to DHPG formation in the liver and kidney, where does initial breakdown of Epi and NE occur in the body?
Recall: what 2 enzymes are used in this step?
Liver, kidney, adrenal medulla
| MAO, COMT
41
Where is serotonin converted to melatonin?
Pineal gland
42
What is the rate-limiting enzyme for melatonin formation?
| When is it active?
N-acetyltransferase
| only at night/in dark; undetectable during day
43
Besides sleep issues, what else can melatonin be used to treat? (not that important)
Seasonal affective disorder, migraines...
44
What's a bad side effect of melatonin?
Potent inhibitor of reproduction - decreased spermatogenesis and testes size in males
45
In the melatonin pw, light information is conveyed to what nucleus?
Through what tract?
- SCN
- Retinohypothalamic tract (RHT)
(The SCN transmits the info the to the pineal gland to regulate circadian activity)
46
What is the half-life of protein/peptide hormones?
2-170 min (much longer than monoamines; longer if bound to transport proteins)
- Most hypothalamic/pituitary hormones in this category
47
What are peptide hormones first synthesized as?
| What special sequence do they contain, and what is it for?
Preprohormones
| - Contains signal peptide sequence (localization to ER)
48
When the signal peptide sequence is cleaved from the preprohormone, what is formed?
Prohormone
49
When does the prohormone because a normal hormone?
| What remains w/the "hormone"?
As its processed/packaged into vesicles
| - Copeptides
50
What is the half-life of steroid hormones?
Several min - several hrs
51
All steroid hormones are derived from a __________ precursor.
Cholesterol
52
Give some eg's of steroid hormone and their locations. (just read)
- Adrenal Cortex: Cortisol (human), mineralocorticoid, DHEA, androstenedione
- Kidney: Vitamin D
- Placenta: progesterone, estriol
- Testis: testosterone
- Ovary: 17-estradiol, progesterone
53
On its way to becoming a steroid hormone, what is cholesterol first converted to?
Where does this occur?
Pregnenolone
| - Chol goes from outer mito to inner mito)
54
What 2 proteins are required for the conversion of cholesterol to prenenolone?
What is the function of each?
StAR and P450scc (desmolase)
- StAR: steroidogenic acute regulatory protein; xports chol from out to inner mito.
- Desmolase/P450scc: Cytochrome P450 side chain cleavage (converts chol to pregnenolone)
55
Where in the cell is pregnenolone converted to other steroid hormones?
ER
56
What are the 4 classes of steroid hormones that pregnenolone can be converted to?
- Glucocorticoids
- Mineralcorticoids
- Androgens
- Estrogens
57
What is "positive feedback"? (in terms of A and B)
| Give some of the few, rare biological eg's of positive feedback.
"A stimulates B stimulates A"
1) Parturition AKA childbirth: Contractions stimulate OXY release from hypo, more contractions stimulate more OXY, birth stops loop.
2) Lactation: Suckling stimulates oxytocin release from hypothalamus, more suckling stimulates more oxytocin, lack of suckling stops loop.
3) Ovulation: LH stimulates estradiol in developing follicle, estradiol stimulates more LH, release of oocyte stops loop
4) Blood clotting: Tissue injury activates platelets, platelets activate more platelets, clotting stops release of signals that activate platelets.
58
What is "negative feedback"? (in terms of A and B)
"A stimulates B inhibits A"
| - E.g. osmoregulation
59
What is an endocrine axis? (what are the 3 parts)
- 3 tiered biological system: hypothalamic neurons, anterior pituitary cells, peripheral endocrine gland
- Hormones can exert feedback to regulate any part of the axis
- Important for dx'ing the cause of endocrine disorder
60
In the endocrine axis, what are long loops?
| What are short loops?
"Endocrine Axis-Driven Negative Feedback"
- Long loop: Peripheral gland hormone feeds back to inhibit pituitary or hypothalamus
- Short loop: Pituitary hormone feeds back to inhibithypothalamus
61
What is affected in primary endocrine dz?
Secondary?
Tertiary?
- Primary: Peripheral gland is the issue
- Secondary: Pituitary is the issue
- Tertiary: Hypothalamus is the issue
62
What is the new term for Feed-Forward?
| What is this?
"Physiological Response-Driven Negative Feedback"
| - Physiological effects of the hormone inhibits original endocrine gland
63
(TRH, hypo) -> (TSH, pit) -> (T4/T3, thyroid)
In "Results of TRH stimulation test to dx cause of hypothyroid sx," what indicates failure at the thyroid, or a primary defect?
- TSH levels?
- Pituitary response to TRH?
- High basal TSH levels
| - Normal pituitary responses
64
(TRH, hypo) -> (TSH, pit) -> (T4/T3, thyroid)
In "Results of TRH stimulation test to dx cause of hypothyroid sx," what indicates failure at the pituitary, or a secondary defect?
- TSH levels?
- Pituitary response to TRH?
- Undetectable basal TSH
| - Lack of pituitary response
65
(TRH, hypo) -> (TSH, pit) -> (T4/T3, thyroid)
In "Results of TRH stimulation test to dx cause of hypothyroid sx," what indicates failure at the hypothalamus, or a tertiary defect?
- TSH levels?
- Low basal TSH levels, followed by delayed/protracted return to baseline
66
?
What sx would you expect to see in Euthyroid sick syndrome?
T4/T3 levels?
TSH levels?
- Hypothyroid symptoms with low T4/T3
| - Normal TSH and thyroid
67
What factors affect levels of circulating hormones?
- Age, weight, time of day, male/female, diet
68
When and how do catecholamine levels change in men and women?
Increase after menopause (late 50s)
69
When and how do glucocorticoid levels change in men and women?
Increase after menopause (late 50s)
70
When and how do testosterone levels change in men?
Spike before puberty, slow decline around age 50
71
When and how do estradiol levels change in women?
Spike before puberty, sharp decline around after menopause (age 50)
72
When and how do adrenal androgen levels change in men and women?
Slower rise to peak in 20s, slow and gradual decline for rest of life
73
Which has a longer half-life, ANP or BNP?
BNP (therefore more useful tool)
74
Normal levels of ANP/BNP can r/o what dz?
CHF
75
How do ANP/BNP levels change w/renal failure and/or heart failure?
Increase
76
How do ANP/BNP levels change w/obesity?
Decrease
77
How do ANP/BNP levels change w/age?
Increase
78
Are ANP/BNP levels higher in men or women?
Women
