BC141: Hormones

Question 1

Synthesis of vitamin D: intermediates

Answer 1

1. 7-dehydrocholesterol (provitamin D)
2. previtamin D3, unstable
3. vitamin D3, stable (cholecalciferol)
4. 25-hydroxycholecalciferol (calcifidiol)
5. 1,25-dihydroxycholecalciferol (calcitriol)

Question 2

Synthesis intermediates of aldosterone:

Answer 2

1. cholesterol (common precursor of all steroidal hormones)
2. pregnenelone
3. progesterone
4. 11-deoxycorticosterone (DOC)
5. corticosterone
6. 18-hydroxycorticosterone
7. aldosterone

Question 3

The precursor of aldosterone that is the first to possess salt-retaining properties

Answer 3

progesterone

Question 4

The common precursor to all steroid hormones

Answer 4

Cholesterol

Question 5

Mineralocorticoids with significant activity

Answer 5

1. aldosterone
2. 11-deoxycorticosterone
3. corticosterone

Question 6

Intermediates of cortisol

Answer 6

1. cholesterol
2. pregnenolone (sometimes from progesterone)
3. 17 alpha-hydroxyprogesterone
4. 11-deoxycortisol
5. cortisol

Question 7

Which step in cortisol synthesis is completed in the mitochondria?

Answer 7

This final step from 11-deoxycortisol to cortisol via the enzyme 11beta-hydroxylase.

Question 8

Main transport of cortisol in blood

Answer 8

70% is transported by transcortin.
- CBG, a cortisol-binding globulin (alpha 1 globulin)

Question 9

Minor forms of cortisol transport in blood

Answer 9

• 20% of cortisol in bound to albumin
• 10% is free (biologically active)

Question 10

The half life of unbound/free/ biologically active cortisol

Answer 10

~ 2 hours

Question 11

T/F cortisol is inactivated by the liver

Answer 11

True

Question 12

Steps for thyroid hormone synthesis

Answer 12

1. iodide trapping
2. oxidation of iodide
3. iodination of tyrosine

Question 13

How does iodide enter the thyroid?

Answer 13

Through the symport (secondary active transporter) found on the basolateral surface of follicular cells.
transporter: Sodium-iodide transporter that pumps 2 Na+ in with 1 I+.

Question 14

What are the cofactors of the Na-I transporter?

Answer 14

ATP-dependent, meaning it is a Na-K ATPase thyroidal I-transporter

Question 15

What happens to iodide once taken up by follicular cells?

Answer 15

activation:
oxidized by hydrogen peroxide through enzyme thyroperoxidase (TPO)

Question 16

Structure of thyroglobulin and site of synthesis

Answer 16

• a globulin made by thyroid follicular cells (locally, not by liver)
• glycosylated: large iodinated globulin glycoprotein

Question 17

Composition of thyroid globuline

Answer 17

2 large subunits: 115 tyrosine residues on each.
- tyrosine residue: potential site of iodination

Question 18

What are the two forms of subunits in thyroglobulin?

Answer 18

Depending on number of iodinated tyrosine residues:
1. MIT (monoiodotyrosine): 1 tyrosine residue iodinated
2. DIT (diiodotyrosine): 2 tyrosine residues iodinated

Question 19

What is the majority of the colloid-contained thyroglobulin?

Answer 19

70% of stored thyroglobulin is inactive, as individual subunits (MIT or DIT)

Question 20

How is thyroglobulin activated?

Answer 20

Not by iodination, but by subunits coupling.
T4: 2 DIT subunits
T3: MIT & DIT subunits

Question 21

What is T4?

Answer 21

tetra-iodo-thyronine (thyroxin): 2 DIT molecules
- 99% of hormone produced by thyroid gland

Question 22

What is T3?

Answer 22

tri-iodo-thyronin

Question 23

How long can T3 and T4 be stored in the colloid to supply the body?

Answer 23

several weeks, bound to thyroglobulin

Question 24

What does TSH do?

Answer 24

stimulate thyroid:
- marked increase in phagolysosome activity of follicular cells
- hydrolysis of thyroglobulin is necessary for the release of amino acid constituents: T3 and T4, it “cuts up” the thyroglubulin from the T3 or T4 segment

Question 25

Which enzymes hydrolyze thyroglobulin and where do the products go?

Answer 25

- proteases and peptidase (class 3, hydrolase) - T4 and T3 are discharged into **extracellular space**

Question 26

Will there be any free MIT and/or DIT in the colloid?

Answer 26

Yes, much will not be utilized and therefore is deionized by enzyme (**deionase**) within the cell.

Question 27

Can T3 be convert to T4?

Answer 27

No, but T4, the less active version, can be T3. This happens in **peripheral tissue** - T3: deionation of 5' carbon

Question 28

Which form has the longer-lasting half-life?

Answer 28

T4: biologically inactive, has a 1/2 life of 4-7 days - T3's 1/2 is a day.

Question 29

Stimulus of renin ## Footnote renin-angiotensin system

Answer 29

1. low bp 2. low sodium 3. SNS/ stress

Question 30

Angiotensinogen (precursor) | type of protein

Answer 30

large alpha 2 globulin

Question 31

ACE action

Answer 31

Angiotensin-converting ensyme cleaves two amino acids from ang. l to produce the octapeptide angiotensin ll.