Adrenal Gland(Functional Anatomy)DANISH HASSANLECTURER, UNIVERSITY OF SARGODHA

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.

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.

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.

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

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%)

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. Mineralocorticoids2. Glucocorticoids3. Sex hormones.

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.

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.

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

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.

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

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.

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).

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.

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

Sex Hormones Adrenal sex hormones are transported by another

special plasma protein known as sex hormone-binding globulin.

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