Quick Notes on Adrenal Medullary Hormones

In this article we will discuss about Adrenal Medullary Hormones. After reading this article you will learn about: 1. Meaning of Adrenal Medullary Hormones 2. Source of Adrenal Medullary Hormones 3. Biosynthesis 4. Secretion 5. Control 6. Catabolism.

Meaning of Adrenal Medullary Hormones:

Adrenal medulla is histologically made up of chromaffin cells. These cells secrete two hormones epinephrine (adrenaline) and nor epinephrine (nor adrenaline). These hor­mones are popularly known as emergency hormone, because they are produced in re­sponse to fight, fright and flight. These in­clude emergencies like shock, cold, fatigue, emotion etc.

Source of Adrenal Medullary Hormones:

Chromaffin cells of adrenal medulla contain chromaffin granules which are responsible for the synthesis and release of medullary hormones by the action of sympathetic ner­vous system.

Biosynthesis of Adrenal Medullary Hormones:

Epinephrine and norepinephrine are chemi­cally known as catecholamine’s since they are amine derivatives of catechol nucleus (dehydroxylated phenyl ring).

Catecholamine’s syntheses occur in following steps:

1. Formation of DOPA from Tyrosine:

Catecholamine’s are derived from the amino acid, phenyl alanine. In the liver phenyl alanine is hydroxylated by phenylala­nine hydroxylase enzyme to tyrosine. Tyrosine is the immediate precursor of catecholamine’s. Tyrosine molecules reach the adrenal medulla through cir­culation.

In chromaffin cells, tyrosine is converted to dihydroxyphenylalanine (DOPA) by the enzyme tyrosine hydroxy­lase. This is the rate limiting enzyme in catecholamine biosynthesis. The activ­ity of this enzyme is regulated in a vari­ety of ways. The most important mecha­nism involves feedback inhibition by the catecholamine’s, which compete with the enzyme for the petridine cofactor by forming a Schiff base with the latter.

Ty­rosine hydroxylase is also competitively inhibited by a series of tyrosine deriva­tives, including α-methyltyrosin. A third group of compounds inhibit tyrosine hy­droxylase by chelating iron and thus re­moving available cofactor (an example is α, α’-dipyridil).

2. Conversion of DOPA to Dopamine:

DOPA is then decarboxylated by the action of aromatic amino acid decarboxylase into dopamine. This enzyme present in all tissues like liver, kidney, brain etc.

3. Dopamine to norepinephrine:

Dopam­ine is then hydroxylated by dopamine β- hydroxylase (DBH) by addition of an – OH group to the side chain carbon (β- carbon adjacent to the phenolic ring), result is the formation of norepinephrine. The conversion takes place within the granule of chromaffin cell.

4. Norepinephrine to Epinephrine:

Nore­pinephrine passes out into the cytoplasm and undergoes methylation by the enzyme phenyl ethanolamine -N-methyl transferase (PNMT). It is noted that nore­pinephrine is the primary amine, whereas epinephrine is the N-methylated sec­ondary amine (Fig. 6.19).

The major product of the adrenal medulla is epinephrine. This compound constitutes about 80% of the catecholamine’s. In con­trast, most of the nor-epinephrine present in the organs innervated by sympathetic nerves is made in-situ.

Secretion of Adrenal Medullary Hormone:

The chromaffin granules contain a number of substances in addition to catecholamine’s, including ATP-Mg⁺⁺, Ca⁺⁺, DBH and the protein chromagranin. Catecholamine’s are released by exocytosis by neural stimulus secretion complying with Ca⁺⁺.

Control of Adrenal Medullary Hormone:

Neural stimulation of adrenal medulla causes the release of catecholamine’s. A variety of stressful conditions like hypoglycemia, hy­poxia, asphyxia, hypotension, exercise fear etc. stimulate the medulla for secretion of these hormones.

Catabolism of Adrenal Medullary Hormone:

Catecholamine’s are rapidly inactivated and metabolised. They are found in plasma in loose association with albumin. The en­zymes catechol-o-methyItransferase (COMT) and monoamine oxydase (MAO) found in many tissues act on catecholamine’s. The metabolic products metaepinephrine, metanephrine and vaniIlyI mandelic acid (VMA) are excreted through urine (Fig. 6.20).