1. The Adrenal Gland
Atif Hassan Khirelsied, Ph.D
,
Department of Biochemistry
Faculty of Medicine
International University of Africa

2. The Adrenal Glands
• The two adrenal glands are
g
located on the anterior
surface above the kidneys.
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• Each gland weighs about 6
grams, the left adrenal is
th l ft d li
longer and thinner.

3. The Adrenal Glands

4. The Adrenal Glands

5. The Adrenal Glands
The adrenal gland is compound gland, comprises
The adrenal gland is compound gland comprises
two different endocrine tissues.
Cross sectioning through the adrenal gland reveals
a pale medulla in the centre surrounded by a
darker cortex.
Each of these two regions produces a distinctly
Each of these two regions produces a distinctly
different group of hormones.

6. The cortex
• It is the outer part of the gland.
• It consists of three concentric
zones of cells, rich in cholesterol.
zones of cells rich in cholesterol
• Each zone has a characteristic arrangement of cells and
contains different set of enzymes, thus differ in their
major hormonal products.

7. The adrenal cortex
• Zona glomerulosa
glomerulosa,
predominantly secretes
mineralocorticoids
(aldosterone).
• Zona fasiculata, the main
source of glucocorticoids
source of glucocorticoids
(cortisol) and androgens.
• Zona reticularis, produces
androgens

8. The Adrenal Gland
• The adrenal medulla (AM) is actually an extension of
The adrenal medulla (AM) is actually an extension of
the sympathetic NS “special ganglion”.
1. The splenic nerve terminates in the AM, innervates
the chromaffin cells.
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2. Chromaffin cells produce the catecholamines.

9. The hormones of the adrenal medulla
• Chromaffin cells produce the catecholamines.
1. Epinephrine
2. Norepinepherine
3. Dopamine.
• Th
They are not essential for life.
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• A
Are required for adaptation to stress (acute ,
i df d i (
chronic).
• Major element for severe stress.

10. The biosynthesis of catecholamines

11. The biosynthesis of catecholamines
Tyrosine hydroxylase
, y yp y ( )
1. Produces L‐3,4‐dihydroxyphenylalanine (L‐DOPA).
2. Is the rate limitting enzyme.
3 Iron‐containing protein[ferric state(Fe2)]
3. Iron‐containing protein[ferric state(Fe )].
4. Exists in soluble and particle forms.
5. Uses molecular oxygen.
5 U l l
6. Requires tetrahydrobiopterin (BH4).

12. The biosynthesis of catecholamines
• Tyrosine hydroxylase inhibitors.
1. Feedback inhibited by its products.
1 Feedback inhibited by its products
2. Can be competitively inhibited by tyrosine derivatives
2 Can be competiti el inhibited b t rosine deri ati es
( e.g., α‐methyltyrosine), used for treatment of
pheochromocytoma.
pheochromocytoma
3. Can also be inhibited by iron‐chelating agents (e.g.,
3 C l b i hibit d b i h l ti t (
αα‐‐bipyridine).
22‐‐bipyridyl

13. The biosynthesis of catecholamines
• Aromatic L‐amino acid (Dopa)
decarboxylase
Synonyms:
– tryptophan decarboxylase,
– 5‐hydroxytryptophan decarboxylase.
It catalyzes several different
decarboxylation reactions:
• L‐DOPA to dopamine
• 5‐HTP to serotonin
• tryptophan to tryptamine

14. The biosynthesis of catecholamines
• Aromatic L‐amino acid (Dopa) decarboxylase
1. Soluble form.
2.
2 Requires pyridoxal phosphate.
Req ires pyridoxal phosphate
3. Is competitively inhibited by α‐methyl dopa.
4. Can also be inhibited by halogenated compounds.
5. Anti‐hypertension drugs (methyl dopa, 3‐
hydroxtyramine, α‐methyl tyrosine, metaraminol)
inhibits this enzyme .

15. The biosynthesis of catecholamines
• Dopamine‐β‐hydroxylase (DBH)
1. Converts dopamine to norepinephrine
p p p
2. Requires ascorbic acid as e‐ donor.
3. Has Cu in active site.
Has Cu in active site.
4. Use fumarate as modulator

16. The biosynthesis of catecholamines
• Phenylethanolamine‐N‐methyl transferase (PNMT)
Phenylethanolamine‐N‐methyl transferase
1. Soluble in cytoplasm.
2. Induced by glucocorticoids.
2 I d db l ti id
3. Uses SAM, methyl donor.

17. The regulation of catecholamines synthesis
1. Stimulated by splanchnic nerve.
1 Stimulated by splanchnic nerve
2. Increases after acute stress by activation of enzymes.
3. Enzymes are induced by chronic stress (corticoids).
3 En mes are ind ced b chronic stress (corticoids)

18. The storage, release and uptake of catecholamines
• Storage .
1. Stored in the chromaffin granules
2. Associated with ATP‐Mg2+ and Ca2+
• Release .
1. By exocytosis (Ca2+‐dependent)
2. Stimulated by cholinergic and β‐adrenergic
3. Inhibited by α‐adrenergic
• Uptake.
Neuronal uptake of the hormone is necessary for:
1. Conservation of the hormone
2. Termination of signal

19. The catecholamines receptors
• α1 .
1. Acts via calcium.
2. Increases glycogenolysis.
3. Smooth muscle contraction (blood vessels, urinogenital
tract).
tract)
• α2.
1. Inhibits cAMP formation.
2. Smooth muscle relaxation (GIT)
3. Smooth muscle contraction (some vascular beds)
4. Inhibits:
1.
1 lipolysis
li l i
2. Renine release
3. Platelets aggregation
4. Insulin secretion

20. The catecholamines receptors
• β1 .
1. Stimulates cAMP formation
2. Stimulates lipolysis
3. Increases mycocardial contraction (rate and force)
• β2.
1. Stimulates cAMP formation
2. Increases smooth muscle contraction (bronchi, blood
vessels, GIT and GUT)
vessels GIT and GUT)
3. Increases:
1. Hepatic gluconeogenesis
p g g
2. Hepatic glycogenolysis
3. Muscle glycogenolysis
4. Release of insulin, glucagon and renin

21. Types of adrenergic receptors
Receptor Effectively Effect of Ligand Physiologic
Binds Binding Effects
α1 Norepinephrine,
Norepinephrine Increased free ↑ vasoconstriction.
vasoconstriction
Epinephrine. calcium ↑ smooth muscle
contraction.
↑ skin and visceral
ki d i l
α2 Norepinephrine, Decreased cyclic arterioles constriction.
Epinephrine. AMP ↑ sphincters and pilomotor
constriction.
↓ insulin secretion

22. Types of adrenergic receptors
Receptor Effectively Effect of Ligand Physiologic
Binds Binding Effects
β1 Epinephrine,
E i hi Increased cyclic
I d li ↑ h t rate
heart t
Norepinephrine AMP ↑ heart strength
↑ lipolysis.
Β2 Epinephrine Increased cyclic ↑ vasodilatation.
AMP ↑ bronchodilatation.
↑ glycogenolysis.
l l i
↑ glycolysis
↑ calorigenesis.
↑ relaxation of intestine, uterus
and bladder wall.

23. The catecholamines mechanism of signaling
• Binding to β1 and β2
Binding to β1 and β2 .
1. Stimulates G‐proteins coupled to adenylate cyclase.
• Binding to α2.
1. Inhibits adenylate cyclase.
• Binding to α1.
1. Is coupled to phospholipase C, increases
1 Is coupled to phospholipase C increases
phosphoinsitol, DAG and Ca2+.

24. The catabolism of catecholamines
1. Have very short t½ (10‐30 sec)
2. Less than 5% is excreted in urine
3. Catabolized by:
1. Catechol‐o‐methyl transferase (
h l h l f (COMT)
)
2. Monoamine oxidase

25. Catecholamine degradation
COMT = Catechol‐o‐methyl transferase, MAO = Monoamine oxidase,
DOPAC = 3,4‐Dihydroxyphenylacetic acid, MHPG = 3‐Methoxy‐4‐hydroxyphenylglycol ,
DOPAC = 3 4 Dihydroxyphenylacetic acid MHPG = 3 Methoxy 4 hydroxyphenylglycol
DHPG = 3,4 dihydroxyphenylglycol,
VMA = Vanillylmandelic acid, HVA = homovanillic acid (HVA,