Book recommended: Medical Physiology by Jaypee

1. Adrenal Gland
(Functional Anatomy)
DANISH HASSAN
LECTURER, UNIVERSITY OF SARGODHA

2. Adrenal Glands
 Called the ‘life-saving glands’ or ‘essential
endocrine glands’.
 It is because the absence of adreno-cortical
hormones causes death within 3 to 15 days and
absence of adreno-medullary hormones,
drastically decreases the resistance to mental
and physical stress.

3.  Functional Anatomy Of Adrenal Glands
 Two adrenal glands
 Each gland is situated on the upper pole of each
kidney.
 Because of the situation, adrenal glands are
otherwise called suprarenal glands.
 Each gland weighs about 4 g.

4.  Parts Of Adrenal Gland
 Made of two distinct parts:
1. Adrenal cortex:
 Outer portion, constituting 80% of the gland
2. Adrenal medulla:
 Central portion, constituting 20% of the gland.
 These two parts are different from each other in
development, structure and functions.

5.  Adrenal medulla develops from the neural crest, which
gives origin to sympathetic nervous system.
 So, its secretions and functions resemble that of
sympathetic nervous system functions resemble that of
sympathetic nervous system.
 Adrenal cortex develops from the mesonephros, which
give rise to the renal tissues.
 It secretes entirely a different group of hormones
known as corticosteroids

6.  Histology Of Adrenal Cortex
 Adrenal cortex is formed by three layers of structure.
 Each layer is distinct from one another.
1. Outer zona glomerulosa (15%)
2. Middle zona fasciculata (75%)
3. Inner zona reticularis (10%)

9.  Hormones Of Adrenal Cortex
 Adrenocortical hormones are steroids in nature,
hence the name ‘corticosteroids’.
 Based on their functions, corticosteroids are
classified into three groups:
1. Mineralocorticoids
2. Glucocorticoids
3. Sex hormones.

10.  Synthesis Of Adrenocortical Hormones
1. All adrenocortical hormones are steroid in nature
and are synthesized mainly from cholesterol that is
absorbed directly from the circulating blood.
2. Synthesis mainly occurs in the mitochondria and
endoplasmic reticulum of the cortical cells
3. They share an initial step in their biosynthesis
(steroidogenesis), which is the conversion of
cholesterol to pregnenolone.

11. 4. Small quantity of cholesterol is also synthesized
within the cortical cells from acetyl coenzyme A
(acetyl-CoA).
5. 80 percent of the cholesterol used for steroid
synthesis is provided by low-density lipoproteins
(LDL) in the circulating plasma.
6. The LDLs, which have high concentrations of
cholesterol, diffuse from the plasma into the
interstitial fluid and attach to specific receptors
contained in structures called coated pits on the
adrenocortical cell membranes.

12. 7. The coated pits are then internalized by
endocytosis, forming vesicles that eventually fuse
with cell lysosomes.
8. An enzyme called cholesterol estrase releases
cholesterol that can be used to synthesize adrenal
steroid hormones.
9. Cholesterol is transferred from the outer
mitochondrial membrane to the inner
mitochondrial membrane by steroidogenic acute
regulatory (StAR) protein

13. 10. Conversion of cholesterol to pregnenolone by
cytochrome P450 side chain cleavage (SCC)
enzyme (P450scc; or cholesterol SCC desmolase)
11. In all three zones of the adrenal cortex, this initial
step in steroid synthesis is stimulated by the different
factors that control secretion of the major hormone
products aldosterone and cortisol.

14.  For example, both ACTH, which stimulates cortisol
secretion, and angiotensin II, which stimulates
aldosterone secretion, increase the conversion of
cholesterol to pregnenolone

17.  An enzymatic defect of 21-hydroxylase accounts for
95% of the genetic abnormalities in adrenal steroid
hormone synthesis
 The second most frequent abnormality in
glucocorticoid synthesis is deficiency of the enzyme
11β-hydroxylase.
 Deficiencies in these enzymes result in impaired cortisol
synthesis, lack of negative feedback inhibition of the
release of adrenocorticotropic hormone (ACTH), high
ACTH levels, and greater stimulation of cholesterol
conversion to pregnenolone.

18.  Because of the lack of negative feedback inhibition of
ACTH release and the resulting high ACTH levels and
greater stimulation of steroidogenesis, the intermediate
metabolites continue to be synthesized, and their
buildup leads to a shunting to the alternate enzymatic
pathways.
 Thus, more pregnenolone is shunted to the DHEA–
androstenedione pathway and more intermediate
metabolites are converted to androgens, resulting in
virilization (presence of masculine traits).

21.  Transport
 Mineralocorticoids
 Transported in blood by binding with plasma
proteins, especially globulins.
 The binding is loose and 50% of these hormones are
present in free form.

22.  Glucocorticoids
 Transported by a special plasma protein known as
glucocorticoids-binding globulin/transcortin.
 94% of glucocorticoids are transported by this
protein
 Whereas about 6% of them are found free in
plasma.
 Albumin plays a very little role in glucocorticoid
transport

23.  Sex Hormones
 Adrenal sex hormones are transported by another
special plasma protein known as sex hormone-
binding globulin.

24.  Fate Of Corticosteroids
 Degraded mainly in the liver.
 Conjugated to form glucuronides and to a lesser
extent, form sulfates.
 About 25% of corticosteroids are excreted in bile
and feces and remaining 75%, in the urine