In this article we will discuss about the Adrenal Medulla and Adrenal Cortex.
Epinephrine and Norepinephrine:
1. These hormones are structurally related to a group of organic compounds known as catechol’s. The aromatic nucleus of these hormones is that of catechol (1, 2- di-hydroxy-benzene) but the amino group is attached to an aliphatic side-chain. Hence, the term catecholamine.
2. 80 per cent of the catecholamine activity is attributed to epinephrine. Naturally occurring epinephrine is the L-isomer. The unnatural D-form is only one-fifteenth active.
3. Epinephrine differs from norepinephrine only in that epinephrine is methylated on the primary amino group of the aliphatic side-chain shown in the figure 31.7.
1. Epinephrine gives a rapid physiologic response to emergencies such as cold, fatigue, shock etc. In this sense, it mobilizes the terms “fight or flight” mechanism.
2. These hormones are effective on parenteral administration. They are destroyed by oxidation when given orally.
3. They increase blood pressure.
4. Epinephrine increases cAMP by activating adenylate cyclase. cAMP stimulates phosphorylase which causes the breakdown of glycogen in the liver resulting in increased blood sugar. Norepinephrine is one-fifth potent in this respect.
5. Epinephrine causes increased breakdown of muscle glycogen to lactic acid, thereby increasing blood lactate.
6. Epinephrine acts on adipose tissue and releases free fatty acids into the circulation.
7. Epinephrine also increases BMR.
8. Epinephrine is an effective stimulant of heart action. It increases the irritability and the rate and strength of contraction of cardiac muscle and increases cardiac output. It causes vasodilatation of the arterioles of the skin and mucous membranes. Norepinephrine has less effect on cardiac output.
9. Epinephrine causes relaxation of the smooth muscles of the stomach, intestine, bronchioles and urinary bladder. This hormone is valuable in the treatment of asthmatic attacks.
In plasma the normal level of epinephrine is <0.1 ng/ml and norepinephrine is <0.5 µg/L.
1. All steroid hormones have a parent ring, i.e. cyclopentanoperhydrophenanthrene ring.
2. Most naturally occurring steroids contain alcohol side-chains and are referred to as sterols.
3. About 50 steroids have been isolated from the adrenal gland, but only a few possess physiologic activity. The most important ones are cortisone, hydrocortisone (Cortisol, 17- hydroxycorticosterone), aldosterone and the two androgens androstenedione and dehydroepiandrosterone. Cortisol is the major free circulating adernocortical hormone in human plasma.
4. A and B rings of the nucleus are joined in a tram or trans and cis configuration. Estrogens do not show such isomerism since their A ring is aromatic.
5. In natural steroids, both the chains attached at C17 and various substitutions at C11 are in the β-configuration.
Demerization of Glucocorticoid Receptor:
1. The amino terminal half contains most of the antigenic sites and has a region that modulates promoter function (trans-activation).
2. The, carboxy terminal half contains the DNA and hormone binding domains.
3. The DNA binding domain is closer to the centre of the molecule, while the hormone binding domain is near the carboxyl terminus. Both of these domains are required for transactivation of gene transcription.
4. A sequence of amino acids in the carboxy terminal regions is required for dimerization of 2 receptor molecules.
5. Two separate regions appear to be necessary for entry of the receptor into the nucleus.
A. The Glucocorticoids:
1. These hormones increase glucose, fatty acids and amino acids in the blood.
2. In the peripheral tissues (muscle and adipose tissues), they cause depletion of protein stores.
3. In adipose tissue, they increase lipolysis and in muscle, they cause depletion of protein stores.
4. They increase alanine-α-ketoglutarate and tyrosine transaminases as well as tryptophan pyrrolase.
5. They increase the key enzymes in the regulation of gluconeogenesis (Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase, fructose-1 6-di-phosphatase and glucose-6- phosphatase).
6. In the liver, they act on the fixation of CO2 at the level of pyruvate carboxylase which is the key enzyme in gluconeogenesis.
7. They are inactive on heart, brain and red cells.
8. They have anti-inflammatory effects and also immunosuppressive effects.
9. They have effects on bone, exocrine secretion, cyclic AMP and stress.
B. The Mineralocorticoids:
1. They increase the absorption of sodium and chloride by the renal tubules and decrease their absorption by the sweat glands, salivary glands, and the gastrointestinal tract.
2. They cause, on administration, increased extracellular fluid volume, increased circulating blood volume and urinary output.
3. Aldosterone also increases the renal clearance of magnesium.
C. Sex Hormones (C-19 Corticosteroids):
1. The adrenocorticosteroids cause retention of nitrogen (a protein anabolic effect), phosphorus, potassium, sodium and chloride. If they are present in excessive amounts, they lead to masculinization in the female.
2. Estrogens and progesterones are produced in small amounts.
Abnormalities of Adrenocortical Function:
A. In humans, degeneration of the adrenal cortex due to tuberculous process or in diabetes and hypothyroidism causes Addison’s disease which shows the following signs:
1. Decreased 17-hydroxy-corticoid and aldosterone excretion.
2. Excessive loss of sodium chloride in the urine.
3. Elevated levels of potassium in the serum.
4. Low blood pressure and low body temperature.
5. Muscular weakness, gastrointestinal disturbances, hypoglycemia, and a progressive brownish pigmentation.
B. Adrenocortical hyper-function is caused by malignant tumors of the cortex. This hyper-function of the cortex causes Cushing’s disease which exhibits the following signs:
1. Hyperglycemia and glycosuria (Diabetogenic effect).
2. Retention of sodium and water followed by edema, increased blood volume and hypertension.
3. Negative nitrogen balance (Protein anti-anabolic effect and gluconeogenesis).
4. Potassium depletion and hypokalemic alkalosis.
A comparison of several different steroid receptors with thyroid hormone receptors revealed a remarkable conservation of the amino acid sequence in regions, particularly in DNA binding domain. Receptors of the steroid/thyroid type constitute a large superfamily. Many related members of this family have no known ligand, so called orphan receptors.