Lecture 2: Hormone Chemistry and Regulation

Question 1

Amines:

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

Answer 1

Amines (half life: 2-3 minutes)

Catecholamines: derived from single tyrosine

Indoleamines: derived from single tryptophan

Question 2

What are the 4 types of hormones?

Answer 2

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

Question 3

Thyroid hormone:

1. What is the half-life
2. State what amino acid is their derivative.

Answer 3

1. LONG half life - 8 days for T4, 24 hours for T3

2. 2 tyrosine molecules

Question 4

What is the half life of the following:

1. Peptides/proteins
2. Steroids

Answer 4

1. 4-170 minutes

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

Question 5

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

Answer 5

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

Question 6

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?

Answer 6

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

then EPINEPHRINE

REQUIRES SYMPATHETIC STIMULATION

Question 7

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

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

Answer 7

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

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

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

HORMONE: inhibits prolactin release from anterior pituitary

Question 8

In the arcuate nucleus,
tyrosine hydroxylase is constitutively active

THEREFORE

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

Answer 8

PROLACTIN

Question 9

What is the tonic inhibitor of prolactin?

Why?

Where do these neurons arise from?

Answer 9

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

Question 10

Dopamingergic neurons arise from_____.

Dopamine is released into _______.

Answer 10

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

Question 11

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

Answer 11

1. NT and hormone
2. Sympathetic
3. B-hydroxylase

Question 12

NE acts through both ___ and ____ receptors.

This is paracrine or autocrine?

Answer 12

NE acts through both alpha- and beta-adrenergic receptors

-PARACRINE AFFECT

Question 13

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

Answer 13

Chromaffin

Question 14

Indoleamines:

1. Rate limiting enzyme is?
2. What are 2 hormones that are indoleamines?

Answer 14

1. Tryptophan Hydroxylase
2. Serotonin
   ( both NT and hormone)
3. Melatonin
   - hormone produced in pineal gland

(rate limiting enzyme = SNA - N acetyl transferase)

Question 15

What converts tryptophan to seratonin?

To melatonin from serotonin?

Answer 15

1. Tryptophan Hydroxylase (TPH)

2. SNA - N acetyltransferase

Question 16

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

What are its functions?

Answer 16

Enterochromaffin

• Vasoconstictor
  Stimulates smooth muscle contraction in intestine

Question 17

What is the function of SSRI’s?

What are the clinical considerations of SSRI’s?

Answer 17

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

Question 18

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

Answer 18

VMA

Vanilylmandelic Acid

Question 19

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

Answer 19

VMA

Vanilylmandelic Acid

• breakdown product of monoamine metabolism

Question 20

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)

Answer 20

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

2. Benzeerazie Cardidopa
   inhibit conversion outside the cell

Question 21

Melatonin:

Converted from _____. Where?

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

Potent inhibitor of ______.

Answer 21

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.

Question 22

Melatonin Secretion:

Light information is conveyed to the SCN via the ______

The SCN transmits the information Where?

Melatonin is undetectable during ____ and peaks when?

Answer 22

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

Question 23

How all are protein hormones made?

Answer 23

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

Question 24

Steroids are all derived from _____.

What are 5 examples of steroid hormones?

Answer 24

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

Question 25

What hormone is associated with the following: 1. Adrenal Cortex: Cortisol (human), 2. Kidney 3. Placenta: 3. Testis: 4. Ovary:

Answer 25

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

Question 26

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

Answer 26

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

Question 27

Steroid hormones are lipophilic or lipophobic? Intra/extracellular? Bounr/free in blood?

Answer 27

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

Question 28

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

Answer 28

ADH/AVP

Question 29

What is an endocrine axis? What makes up the endocrine axis?

Answer 29

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

Question 30

Hypothalamic hormones use _____ feedback. Define short loop hormone feedback. Define "long loop" hormone feedback.

Answer 30

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

Question 31

What are 2 types of negative feedback?

Answer 31

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

Question 32

What are 4 examples of positive feedback?

Answer 32

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

Question 33

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

Answer 33

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.

Question 34

Primary failure occurs at the level of what? (Thyroid/ TRH/TSH/T4/T3) What levels are high?

Answer 34

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

Question 35

Describe how the thyroid hormone response normally progresses

Answer 35

Hypothalamus releases TRH - TRH stimulates TSH in the anterior pituitary - TSH stimulates the release of T4/T3 in the THYROID

Question 36

If there is failure at the pituitary (secondary) What are the affects?

Answer 36

1. No response to TRH 2. Undetectable TSH STRAIGHT LINE -PITUITARY is not responding to TRH!! therefore no TSH made FLAT LINE = SECONDARY LEVEL

Question 37

Failure at hypothalamus (tertiary) What is the response?

Answer 37

Normal response or protracted return to baseline

Question 38

What happens in Euthyroid Sick syndrome?

Answer 38

Euthyroid sick syndrome: Hypothyroid symptoms with low T4/T3 Normal TSH and thyroid Euthyroid = profile is normal (Not on the test!!!!)  rare

Question 39

Normal range of hormones depends on what 4 factors?

Answer 39

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

Question 40

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?

Answer 40

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