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THE ADRENAL GLANDS

They lie at the superior poles of the two kidneys. Each gland is composed of two distinct parts:

1. Adrenal Cortex – 80%

2. Adrenal Medulla- 20%

CORTICOSTERIODS – group of hormones secreted by the adrenal cortex. These are synthesized from the steroid Cholesterol. The following are the ADRENOCORTICAL HORMONES:

1. Mineralocorticoids – affect electrolytes of the ECF – Sodium and Potassium

2. Glucocorticoids – Exhibit an important effect in increasing blood glucose concentration

3. Androgenic hormones

ALDOSTERONE – principal mineralocorticoidCORTISOL – principal glucocorticoid

LAYERS OF ADRENAL CORTEX AND SECRETION

1. Zona Glomerulosa

- constitutes about 15% of the adrenal cortex

- cells are the only ones secreting Aldosterone

- they contain enzyne aldosterone synthase necessary for synthesis of aldosterone

- secretion is controlled by ECF conc. of Angiotensin II and Potassium

2. Zona Fasciculata

- constitutes about 75% of the adrenal cortex- middle and widest layer- secretes the glucocorticoids cortisol and

corticosterone and small amounts of adrenal androgens and estrogens- secretion is controlled by hypothalamic-pituitary axis via adrenocorticotropic hormone (ACTH)

3. Zona Reticularis

- secretes the adrenal androgen hydroepiandrosterone (DHEA) and androstenedione and small amounts of estrogen and some glucocorticoids

- secretion is regulated by ACTH and other factor such as cortical androgen-stimulating hormone from the pituitary

More Important Glucocorticoid Hormones including Synthetic ones:

1. Mineralocorticoids

- Aldosterone (very potent, accounts for 90% of all mineralocorticoid activity- Desoxycorticosterone (1/30 as potent as aldosterone, but very

small quantities secreted- Corticosterone (slight minralocorticoid activity)- 9a-Fluococortisol (synthetic, slightly more potent than aldosterone)- Cortisol (very slight mineralocorticoid activity, but large

quantity secreted- Cortisone (synthetic, slight mineralocorticoid activity)

2. Glucocorticoid

- Cortisol (very potent, accounts for about 95% of all glucocorticoid activity

- Corticosterone (provides 4% of total glucocorticoid) activity, much less potent than cortisol)

- Cortisone (synthetic, almost as potent as cortisol)- Prednisone (synthetic, four times as potent as cortisol)- Methyprednisone (synthetic, five tmes as potent as

cortisol)- Dexamethasone (synthetic, 30 times as potent as

cortisol)

The Intense Glucocorticoid Activity of Dexamethasone, has almost zero mineralocorticoid activity, thus is important drug for stimulating specific glucocorticoid activity

FUNCTIONS OF MINERALOCORTICOID – Aldosterone

1. Renal and Circulatory Effects of Aldosteronea. Aldosterone Increases Renal Tubular Reabsorption

of Sodium and Secretion of Potassium – especially in the principal cells of the collecting tubules, and to lesser extent in the distal tubules and collecting ducts

b. Excess Aldosterone Increases ECF Volume and Arterial Pressure but Has Only a Small Effect on Plasma Sodium Concentration

c. Excess Aldosterone Causes Hypokalemia and Muscle Weakness; Too little Aldosterone Causes Hyperkalemia and Cardiac Toxicity

Hypokalemia causes severe muscle weakness caused by alteration of the electrical excitability of the nerve and muscle fiber membranes which prevents transmission of normal action potential

Deficient Aldosterone – results to cardiac toxicity, including weakness of heart contraction and development of arrhythmia

C. Excess Aldosterone Increases Tubular Hydrogen Ion Secretion with Resultant Mild Alkalosis

- secretion hydrogen ion in exchange for sodium in the intercalated cells of the cortical collecting tubules

2. Aldosterone Stimulates sodium and Potassium Transport in Sweat Glands, Salivary

Glands and Intestinal Epithelial Cells

- same effects as it has on the renal tubules

Cellular Mechanism of Aldosterone Action

1. Aldosterone diffuses readily to the interior of the tubular epithelial cells

2. In the cytoplasm of the tubular cells, aldosterone combines with specific cytoplasmic receptor protein

3. Aldosterone-receptor complex diffuses into the nucleus, inducing RNA to form messenger RNA

4. The mRNA diffuses back into the cytoplasm operating in conjunction with the ribosomes causes protein formation

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