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).
