7.2. The function of the adrenal cortex. Flashcards
I. Adrenal gland (suprarenal glands)
1. Describe the structure of adrenal gland?
Bilateral structures located above the kidneys
- Outer cortex (75%) (~4g):
+) Composed of cortical cells
+) Synthesize adrenocortical hormones
- Inner medulla (25%):
+) Composed of chromaffin cells
+) Synthesize NE + E
I. Adrenal gland (suprarenal glands)
2. Describe the blood supply of adrenal gland
Blood supply: flows from cortex to medulla
- Important, because medulla will get information about the cortex and the cortex can control NE + E synthesis of medulla
I. Adrenal gland (suprarenal glands)
3A. What are the 3 zones of cortex?
1) Zona glomerulosa (15%): produce
mineralocorticoids (ex: aldosterone)
MOST IMPORTANT
2) Zona fasciculata (75%): produce glucocorticoids (ex: cortisol)
3) Zona reticularis (10%): produces
androgens (ex: DHEA[S])
I. Adrenal gland (suprarenal glands)
3B. What does Zona glomerulosa produce?
1) Zona glomerulosa (15%): produce
mineralocorticoids (ex: aldosterone)
MOST IMPORTANT
I. Adrenal gland (suprarenal glands)
3C. What does Zona fasciculata produce?
Zona fasciculata (75%): produce glucocorticoids (ex: cortisol)
I. Adrenal gland (suprarenal glands)
3D. What does Zona reticularis produce?
Zona reticularis (10%): produces
androgens (ex: DHEA[S])
II. Hormones
1. What are 3 types of hormones produced by adrenal gland?
- Mineralocorticoids (ex: aldosterone)
- Glucocorticoids (ex: cortisol)
- Androgens (ex: DHEA[S])
I. Adrenal gland (suprarenal glands)
2. What are the features of Mineralocorticoids?
Will affect/control the plasma minerals
- Aldosterone
- DOC = deoxycorticosterone
- (cortisol) – has some mineralocorticoid activity
I. Adrenal gland (suprarenal glands)
3. What are the features of Glucocorticoids?
Will affect blood plasma glucose concentration
- Cortisol
- Cortisone (11β HSD1 – convert ineffective cortisone to effective cortisol)
- Corticosterone
- Synthetic glucocorticoids (clinical importance: medication)
I. Adrenal gland (suprarenal glands)
3. What are the features of Androgens?
Not really hormones, but precursors
- DHEA (S) -> (dehydroepiandrosterone) ->precursor of androgens + estrogens
III. Biosynthesis of hormones
1. All of the adrenocortical hormones are ____
Steroids (hormones)
III. Biosynthesis of hormones
2. What are the feature of adrenocortical hormones?
- All of the adrenocortical hormones are steroids (hormones)
- Hydrophobic: can cross the PM by passive diffusion
- No storage of these hormones
=> They are synthesized from cholesterol-ester, which is stored in lipid droplets
=> Source of cholesterol:
LDL (low density lipoproteins)
De novo synthesis (from acetate)
III. Biosynthesis of hormones
3. Are there any storage for adrenocortical hormones?
- No storage of these hormones
III. Biosynthesis of hormones - Enzyme responsible for biosynthesis
4. What does Regulation of hormone secretion mean?
Regulation of hormone secretion means regulation of amount + activity of enzymes.
III. Biosynthesis of hormones - Enzyme responsible for biosynthesis
5. What are the 2 enzyme families for Biosynthesis of hormones?
1) CYP– cytochrome p450 oxidases
2) HSD– hydroxysteroid dehydrogenase
III. Biosynthesis of hormones - Enzyme responsible for biosynthesis
6. What is the role of CYP11 A1?
Enzyme responsible for the cleavage of the side-chain of the cholesterol
- Catalyze the cholesterol pregnenolone (reaction occurs in the mitochondria)
III. Biosynthesis of hormones - Enzyme responsible for biosynthesis
7. How can the cholesterol get into the mitochondria from the cytoplasm?
III. Biosynthesis of hormones - Zona glomerulosa cells (mineralocorticoids)
8. What is the role of CYP11B2?
CYP11B2 = aldosterone synthase, 3 reactions/activities:
1) 11-hydroxylase activity
2) 18-hydroxylase activity
3) 18 oxidase activity
=> NO CYP17 ENZYME!
III. Biosynthesis of hormones - Zona glomerulosa cells (mineralocorticoids)
9. Make a schematic diagram of aldosterone production
III. Biosynthesis of hormones - Zona glomerulosa cells (mineralocorticoids)
10. What is/are the enzyme(s) in Zona glomerulosa cells ?
CYP11B2
III. Biosynthesis of hormones - Zona fasciculata cells (glucocorticoids)
11. What is/are the enzyme(s) appear in Zona fasciculata cells (glucocorticoids)?
CYP17
III. Biosynthesis of hormones - Zona fasciculata cells (glucocorticoids)
12. Make the schematic diagram of cortisol production
CYP17 + CYP11B1 cortisol
III. Biosynthesis of hormones
13A. What happen if CYP11B2 is genetically modified (no activity)?
If CYP11B2 is genetically modified (no activity), it will only effect the synthesis of the aldosterone
III. Biosynthesis of hormones
13B. What happen if CYP21A2 is genetically modified (no activity)?
if CYP21A2 is modified, it will affect both aldosterone + cortisol biosynthesis
III. Biosynthesis of hormones - Zona reticularis
14. Describe the process of hormones biosynthesis in Zona reticularis
- Here the CYP17 has both hydroxylase + lyase activity
- DHEA(S) => androstenedione (precursor for testosterone + estradiol in the gonads)
III. Biosynthesis of hormones
15. Make a general schematic diagram for hormones biosynthesis in adrenal gland
IV. Hormone secretion and transport
1. What are the common features of cortisol and aldosterone?
Both cortisol and aldosterone are hydrophobic materials which require plasma binding proteins to keep them in the blood plasma
IV. Hormone secretion and transport
2. What are the features of cortisol?
- 90% bound to CBG (corticosteroid binding globulin = transcortin)
- 7% bound to albumin
- 3-4% free (equilibrated with hormone concentration in the cytoplasm)
- Thalf (half-life) = 60-90 min
[cortisol]Total»_space;(1000x)[aldosterone]Total
[cortisol]free >(100x) [aldosterone]free
IV. Hormone secretion and transport
3. What are the features of Aldosterone?
- 60% bound to albumin + CBG
- 40% free (hormone-fraction)
- Thalf (half-life) = 20 min
V. Synthetic glucocorticoids
1. What are examples of Synthetic glucocorticoids?
Examples: methylprednisolone (GC activity = 10) and dexamethasone (GC activity = 20)
- Elimination from blood plasma: (1) mainly in the liver (2) oxidation, conjugation
VI. What are the features of Receptors for adrenocorticol hormones?
VII. Aldosterone
1. What are the receptor and target cells for Aldosterone?
- Receptor: mineralocorticoid receptor (MCR)
- Target cells:
- Principal cells in the kidney (nephrons)
- Exocrine glands (duct cells in sweat/salivary glands)
- Colon (epithelial cells)
VII. Aldosterone
2. What does mineralocorticoid receptor (MCR) bind to?
MCR binds to aldosterone (MC), but it can also bind to cortisol (GC)PROBLEM, because of the free hormone concentration
- [cortisol]free >(100x) [aldosterone]free, therefore the receptors will always be activated by the huge concentration of cortisol
VII. Aldosterone
3. How can the target cells detect the increase of aldosterone?
- Target cells will eliminate the cortisol
- 11β-HSD2 will catalyze cortisol => cortisone (=cannot bind to MCR)
- Aldosterone will then be the only hormone that can activate the receptor