Lecture 2: Hormone Chemistry and Regulation Flashcards

1
Q

Amines:

  1. What is the half-life
  2. State two examples and their derivative amino acid.
A

Amines (half life: 2-3 minutes)

Catecholamines: derived from single tyrosine

Indoleamines: derived from single tryptophan

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2
Q

What are the 4 types of hormones?

A
  1. Amines
  2. Thyroid Hormones
  3. Peptides/Proteins
  4. Steroids
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3
Q

Thyroid hormone:

  1. What is the half-life
  2. State what amino acid is their derivative.
A
  1. LONG half life - 8 days for T4, 24 hours for T3

2. 2 tyrosine molecules

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4
Q

What is the half life of the following:

  1. Peptides/proteins
  2. Steroids
A
  1. 4-170 minutes

2. minutes to several hours - bound to binding proteins in the blood

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5
Q

State the following for catecholamines & indoleomines:

  1. Half life (long or short)
  2. How do they travel in the blood?
  3. What is their main difference
A
  1. Half life is VERY short
  2. Travel FREELY in the blood
    - always bind to membrane receptor to activate messenger signaling pathways
  3. Main difference is SYNTHESIS
  4. tyrosine or tryptophan
  5. tyrosine hydroxylase or tryptophan hydroxylase

Catecholamines = SINGLE tyrosine

Indoleamines = single TRYPTOPHAN

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6
Q

What are some example of tyrosine derived CATECHOLAMINES?

What is the rate limiting enzyme?

What is it converted to from tyrosine?

What is the next precursor?

What kind of stimulation is required?

A
  1. Dopamine
    Norepinephrine
    Epinephrine
  2. Tyrosine Hydroxylase
  3. L-DOPA
  4. Dopamine
    - then Norepinephrine
    (in adrenal medulla)

then EPINEPHRINE

REQUIRES SYMPATHETIC STIMULATION

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7
Q

What are the 2 body organs that dopamine is made in?

What is the action of dopamine in these two areas? (NT or hormone)?

A
  1. Brain
    - Substantia Nigra (parkinsons)
    - Arcuate Nucleus
    - VTA

NEUROTRANSMITTER
- regulates multiple brain functions such as reward/attention mood

  1. Adrenal Gland:
    - adrenal medulla converted to NE!!

HORMONE: inhibits prolactin release from anterior pituitary

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8
Q

In the arcuate nucleus,
tyrosine hydroxylase is constitutively active

THEREFORE

Dopamine is produced at high levels and released into blood
tonically inhibits ______ release

A

PROLACTIN

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9
Q

What is the tonic inhibitor of prolactin?

Why?

Where do these neurons arise from?

A
  1. DOPAMINE
  2. tyrosine hydroxylase is consitutivly active in the Arc. Nucleus
  3. ARCUATE NUCLEUS
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10
Q

Dopamingergic neurons arise from_____.

Dopamine is released into _______.

A

Arcuate Nucleus

Hypophysial capillary bed

-Dopaminergic neurons in the arcuate are distinct from those in other parts of the brain – TH is constitutively active maintaining high DA concentrations in

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11
Q

Norepinephrine:

Functions as what?

Requires _____ nervous system stimulation

Most tissue concentrations equal that of the synapse – conversion takes place primarily in neurons

_______ catalyzes reaction:
DOPAMINE to NOREPINEPHRINE

A
  1. NT and hormone
  2. Sympathetic
  3. B-hydroxylase
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12
Q

NE acts through both ___ and ____ receptors.

This is paracrine or autocrine?

A

NE acts through both alpha- and beta-adrenergic receptors

-PARACRINE AFFECT

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13
Q

_______ cells of adrenal medulla are homologous to postsympathetic neurons – release hormone into blood

A

Chromaffin

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14
Q

Indoleamines:

  1. Rate limiting enzyme is?
  2. What are 2 hormones that are indoleamines?
A
  1. Tryptophan Hydroxylase
  2. Serotonin
    ( both NT and hormone)
  3. Melatonin
    - hormone produced in pineal gland

(rate limiting enzyme = SNA - N acetyl transferase)

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15
Q

What converts tryptophan to seratonin?

To melatonin from serotonin?

A
  1. Tryptophan Hydroxylase (TPH)

2. SNA - N acetyltransferase

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16
Q

Most (95%) of the serotonin in the body is produced by _______ cells in gut

What are its functions?

A

Enterochromaffin

  • Vasoconstictor
    Stimulates smooth muscle contraction in intestine
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17
Q

What is the function of SSRI’s?

What are the clinical considerations of SSRI’s?

A

Increases the concentration of serotonin at the synaptic cleft.

Used clinically to treat depression and other related mental health disorders

Clinical Considerations:

Physiological basis of depression is not well understood
Desensitization/downregulation of postsynaptic receptors
Negative feedback – less serotonin produced in presynaptic cells

18
Q

What can be measured in the urine to see if someone is overproducing catecholamines?

A

VMA

Vanilylmandelic Acid

19
Q

What can be measured in the urine to see if someone is overproducing catecholamines?

A

VMA

Vanilylmandelic Acid

  • breakdown product of monoamine metabolism
20
Q

What is the function of monoamine oxidase?

What inhibits deactivation of L-Dopa outside the cell?

What inhibits conversion outside the cell?
(of dopamine to L-DOpa)

A

Catalyzes oxidative deamination of all monoamines

MAOA and MAOB are both present in humans

MAOIs (e.g. Nardil) were one of the first drugs to treat depression – no longer first choice

1.Entacapone
inhibit the deactivation outside the cell

  1. Benzeerazie Cardidopa
    inhibit conversion outside the cell
21
Q

Melatonin:

Converted from _____. Where?

______ is the rate limiting enzyme and is most active during the night.

Potent inhibitor of ______.

A
  1. Seratonin - n the pineal gland
  2. N- acetyltransferase
  3. Reproduction, – causes decreased spermatogenesis and testis size in males.

Used therapeutically for variety of conditions including insomnia, jet lag, seasonal affective disorder, migrane, etc.

22
Q

Melatonin Secretion:

Light information is conveyed to the SCN via the ______

The SCN transmits the information Where?

Melatonin is undetectable during ____ and peaks when?

A
  1. retinohypothalamic tract (RHT).
  2. pineal gland to regulate its circadian activity.
  3. Daytime, in the middle of the night.
23
Q

How all are protein hormones made?

A

Gene
Transcribed to mRNA
mRNA has SIGNAL sequence (direct the mRNA to the ER after translation), HORMONE, and COPEPTIDE sequence (all hormones have copeptides)
get preprohormone when signal peptide is still present
cleaved and degraded = PROHORMONE ( copeptide + hormone only)
Processed and packaged in the golgi
Packaged with a COPEPTIDE (can be used as an indicitor to see how well the cells are functioning  ex: beta cells in diabetes) since copeptiddes hang around much longer

24
Q

Steroids are all derived from _____.

What are 5 examples of steroid hormones?

A
  1. CHOLESTEROL.
  2. Adrenal Cortex: Cortisol (human), mineralocorticoid, DHEA, androstenedione
  3. Kidney: Vitamin D
  4. Placenta: progesterone, estriol
  5. Testis: testosterone
  6. Ovary: 17-estradiol, progesterone
25
Q

What hormone is associated with the following:

  1. Adrenal Cortex: Cortisol (human),
  2. Kidney
  3. Placenta:
  4. Testis:
  5. Ovary:
A
  1. Adrenal Cortex: Cortisol (human), mineralocorticoid, DHEA, androstenedione
  2. Kidney: Vitamin D
  3. Placenta: progesterone, estriol
  4. Testis: testosterone
  5. Ovary: 17-estradiol, progesterone
26
Q

What transports cholesterol from the outer mitochondria to the inner mitochondria?

A

StAR

-cholesterol from outer mitochondria  INNER MITOCHONDRIA  StAR transports cholesterol into inner mitochondria (stimulated by other hormones)  get PREGNENOLONE (precursor to progesterone, DHEA, etc)

27
Q

Steroid hormones are lipophilic or lipophobic?

Intra/extracellular?

Bounr/free in blood?

A
  1. lipophilic
  2. intracellular
  3. BOUND in the blood (SLOW)
  4. since all are nuclear transcription factors
28
Q

What is an example of a hormone that exhibits negative feedback?

A

ADH/AVP

29
Q

What is an endocrine axis?

What makes up the endocrine axis?

A

Three tiered biological system:

  1. hypothalamic neurons
  2. anterior pituitary cells
  3. peripheral endocrine gland

Hormones can exert feedback to regulate any part of the axis

Important for diagnosing cause of endocrine disorder

30
Q

Hypothalamic hormones use _____ feedback.

Define short loop hormone feedback.

Define “long loop” hormone feedback.

A

NEGATIVE

  1. “Short loop” – hormone feedback from pituitary to hypothalamus

2.“Long loop” – hormone feedback is at level of hypothalamus/ pituitary
from the peripheral gland

31
Q

What are 2 types of negative feedback?

A
  1. Physiological response driven
    - circulating component of the hormone inhibit the endocrine gland
  2. Hypothalamic Axis
    - involves hormone and the pituitary gland as well as the hypothalamus
32
Q

What are 4 examples of positive feedback?

A
  1. Partuition
  2. Lactation
  3. Ovulation
  4. Blood clotting
33
Q

State which type of feedback the following use and how they function/what stops the loop.

  1. Partuition
  2. Lactation
  3. Ovulation
  4. Blood clotting
A

Partuition – childbirth
Contractions (smooth muscle of uteris) stimulate oxytocin release from hypothalamus —more contractions stimulate more oxytocin – birth stops loop.

Lactation (ALSO OXYTOCIN DRIVEN)
Suckling stimulates oxytocin release from hypothalamus —more suckling stimulates more oxytocin – lack of suckling stops loop.

Ovulation
LH stimulates estradiol in developing follicle – estradiol stimulates more LH – release of oocyte stops loop

Blood clotting
Tissue injury activates platelets — platelets activate more platelets – clotting stops release of signals that activate platelets.

34
Q

Primary failure occurs at the level of what?

(Thyroid/ TRH/TSH/T4/T3)

What levels are high?

A

Failure at Thyroid

-Primary defect = high baseline TSH due to loss of negative feedback (low T3), normal pit response to TRH.

35
Q

Describe how the thyroid hormone response normally progresses

A

Hypothalamus releases TRH

  • TRH stimulates TSH in the anterior pituitary
  • TSH stimulates the release of T4/T3 in the THYROID
36
Q

If there is failure at the pituitary (secondary)

What are the affects?

A
  1. No response to TRH
  2. Undetectable TSH

STRAIGHT LINE
-PITUITARY is not responding to TRH!! therefore no TSH made
FLAT LINE = SECONDARY LEVEL

37
Q

Failure at hypothalamus (tertiary)

What is the response?

A

Normal response or protracted return to baseline

38
Q

What happens in Euthyroid Sick syndrome?

A

Euthyroid sick syndrome:

Hypothyroid symptoms with low T4/T3
Normal TSH and thyroid

Euthyroid = profile is normal (Not on the test!!!!)  rare

39
Q

Normal range of hormones depends on what 4 factors?

A
AGE - change over lifetime
BODY WEIGHT**
TIME OF DAY
MALE/FEMALE – ex: BNP levels vary 
DIET
40
Q

ANP and BNP are made where? What is their function?

Which has a longer half life?

Higher levels are associated with what?

Lower levels with?

This increases with _____.

Higher levels in men or women?

A
  1. HEart
  2. BP regulator

BNP – longer half-life than ANP making it a useful diagnostic tool

Normal levels can rule out congestive heart failure

Higher levels with heart and renal failure

Lower levels with obesity

Increases with age

Higher levels in women