Adrenal gland (Adrenal hormones and their production

CORTICAL HORMONES AND
ADRENAL MEDULLA
ILKIN BAKIRLI
SMU GROUP C

STRUCTURE
 LOCATED AT THE SUPERIOR POLES OF THE 2 KIDNEYS
 RETROPERITONEAL
 DIRECTLY BELOW THE DIAPHRAGM
 2 ENDOCRINE ORGANS INSIDE THE ADRENAL GLAND
 OUTER CORTEX
 INNER MEDULLA
 DIFFERENT EMBRYONIC ORIGINS
 4GRAMS
 5CM X 3CM DIMENSIONS
 FATTY CAPSULE SURROUNDING IT

ADRENAL CORTEX
 80% OF THE GLAND
 OUTER LAYER
 3ZONES;
ZONA GLOMERULOSA- PYRAMIDAL CELLS
ZONA FASCICULATA- POLYHEDRAL CELLS
ZONA RETICULARIS- SMALL POLYHEDRAL CELLS
 SECRETES; GLUCOCORTICOIDS, MINERALOCORTICOIDS
AND ANDROGENS RESPECTIVELY
 EMBRYONIC ORIGIN;
DERIVED FROM INTERMEDIATE MESODERM
 BLOOD SUPPLY;
PHRENIC AND RENAL ARTERIES

CLASSIFICATION AND STRUCTURE OF HORMONES
 DERIVATIVES OF CHOLESTEROL
 THEY CONTAIN CYCLOPENTANOPERHYDROPHENANTHRENE NUCLEUS
 3 TYPES OF HORMONES:
I) C21 STEROIDS 2 CARBON SIDE CHAIN
II) C19 STEROIDS KETO OR HYDROXYL GROUP
III) C18 STEROIDS KETO OR HYDROXYL GROUP+ ANGULAR METHYL
 ADRENAL CORTEX SECRETES MOSTLY C21 AND C19
 C19 ANDROGENIC EFFECT
 C21 MINERALOCORTICOID OR GLUCOCORTICOID EFFECTS

SECRETED STEROIDS
 MINERALOCORTICOID ALDOSTERONE AND DEOXYCORTICOSTERONE
 GLUCOCORTICOID CORTISOL AND CORTICOSTERONE
 ANDROGENS DEHYDROEPIANDRSTERONE (DHEA) AND ANDROSTENEDIONE
 DEHYDROEPIANDROSTERONE IS CONJUGATED TO SULPHUR
 EVERY OTHER SECRETED STEROID IS UNCONJUGATED
 ESTROGENS FROM ADRENAL ANDROSTENEDIONE

STEROID BIOSYNTHESIS
 CHOLESTEROL PRECURSOR, FROM ACETATE OR LDL
 ESTERIFIED AND STORED IN FAT DROPLETS
CHOLESTEROL ESTER HYDROLASE
 TRANSPORTED TO MITOCHONDRIA
 CONVERTED INTO PREGNENOLONE,
CHOLESTEROL DESMOLASE
 DEHYDROGENATED TO PROGESTERONE IN SER
 3B-HYDROXYSTEROID DEHYDROGENASE
ALSO CATALYSES 17A-HYDROXYPREGNENOLONE TO 17A-HYDROYPROGESTERONE
AND DEHYDROEPIANDOROSTERONE TO ANDROSTENEDIONE
 (PREGNENOLONE 17A-HYDROXYPREGNENOLONE)
(PROGESTERONE 17A-HYDROXYPORGESTERONE)

 HYDROXYLATION OF PROGESTERONE TO 11-DEOXYCORTICOSTERONE
AND 17A-HYDROXYPROGESTERONE TO 11- DEOXYCORTISOL
 11-DEOXYCORTICOSTERONE AND DEOXYCORTISOL ARE 11-HYDROXYLATED
TO FORM CORTICOSTERONE AND CORTISOL
BY 11B-HYDROLASE IN ZONA FASCICULATA AND ZONA RETICULARIS
 ALDOSTERONE SYNTHASE IN ZONA GLOMERULOSA
LACKS 11B-HYDROXYLASE AND 17A-HYDROXYLASE
SUMMARY
 ZONA GLOMERULOSA MAKES ALDOSTERONE BUT FAILS TO MAKE
CORTISOL OR SEX HORMONES
 ZONA FASCICULATA HAS MORE 3B-HYDROXYSTEROID DEHYDROGENASE
MAKES MORE CORTISOL AND CORTICOSTERONE
 ZONA RETICULARIS HAS MORE 17A-HYDROXYLASE
MAKES MORE ANDROGENS AND DEHYDROEPIANDOSTERONE+SULFATE

TRANSPORT, METABOLISM AND EXCRETION OF ADRENOCORTICAL
HORMONES
GLUCOCORTICOIDS
 CORTISOL IS BOUND TO A-GLOBULIN CALLED TRANSCORTIN OR CBG
HALF LIFE IN BLOOD IS 60-90MIN
13.5UG/DL CORTISOL IN PLASMA
CBG INCREASES DURING PREGNANCY, CIRRHOSIS, NEPHROSIS
THIS INCREASES ACTH SECRETION FROM PITUITARY GLAND
METABOLISED IN LIVER, REDUCED TO TETRAHYDROCORTISOL, CONJUGATED TO GLUCURONIC ACID
CORTISOL CORTICOSTERONE BY 11B-HYDROXYSTEROID DEHYDROGENASE
10% CONVERTED INTO 17-KETOSTEROIDS
15% EXCRETED IN STOOL
 CORTICOSTERONE’S HALF LIFE: 50MIN
METABOLISM IS SIMILAR TO CORTISOL, BUT DOES NOT FROM KETOSTEROIDS.

ALDOSTERONE:
 BOUND TO PROTEINS
HALF LIFE: 20MINS
0.006UG/DL IN PLASMA
IN LIVER CONVERTED INTO TETRAHYDROGLUCURONIDE AND TO 18-GLUCURONIDE
CONVERTED INTO FREE ALDOSTERONE BY HYDROLYSIS AT PH 1.0
>1% IN URINE
5% ACID LABILE CONJUGATE
40% TETRAHYDROGLUCORONIDE
17-KETOSTEROIDS
 TESTOSTERONE IS CONVERTED INTO THIS
DAILY 15MG EXCRETION IN MALE
10MG EXCRETION IN FEMALE
2/3 OF URINARY KETOSTEROIDS SECRETED BY ADRENAL
1/3 IS OF TESTICULAR ORIGIN
UNCONJUGATED ETHICHOLANOLONE CAN CAUSE FEVER (“ETIOCHOLANOLONE FEVER”)

EFFECTS OF THE HORMONES:
ANDROGENS: MASCULINIZING EFFECTS
PROTEIN ANABOLISM AND GROWTH
TESTOSTERONE MOST ACTIVE ANDROGEN
TESTOSTERONE INTO DIHYDROTESTESTERONE
ESTROGENS: ANDROSTENEDIONE CONVERTED TO TESTOSTERONE AND ESTROGENS
IMPORTANT SOURCE OF ESTROGEN IN MEN AND POST MENOPAUSAL WOMEN
GLUCOCORTICOIDS: CORRECT METABOLIC ABNORMALITIES
INCREASE HEPATIC GLYCOGENESIS, INCREASE PROTEIN CATABOLISM, PLASMA GLUCOSE LEVEL RISE
INHIBIT ACTH SECRETION
RESTORE VASCULAR REACTIVITY
REPAIR WATER INTOXICATION
DECREASE CIRCULATING EOSINOPHILS, LYMPHOCYTE AND BASOPHILS
INCREASE NEUTROPHILS, PLATELETS AND RBCS,
INHIBIT INFLAMMATORY RESPONSE TO TISSUE INJURY

MINERALOCORTICOID: INCREASE ABSORPTION OF NA+
RETENTION OF NA+ IN ECF
ACT ON P CELLS OF KIDNEY
NA+ IS EXCHANGED FOR K+ AND H+ IN RENAL TUBULES
ROLE IN SALT BALANCE
ENZYME DEFICIENCIES
 CONGENITAL ADRENAL HYPERPLASIA: DUE TO INCREASE IN ACTH SECRETION
 CHOLESTEROL DESMOLASE DEFICIENCY: PREVENTS PROGESTERONE PLACENTA FORMATION
 CONGENITAL LIPOID ADRENAL HYPERPLASIA: ACCUMULATION OF LIPID DROPLETS
 HYPOSADIAS: ALDOSTERONE DEFICIENCY, URETHRA IS ON UNDER SIDE, NOT ON TIP OF PENIS

REGULATION OF SECRETION
GLUCOCORTICOIDS:
1. ACTH: BASAL AND INCREASED SECRETION PROVOKED BY STREES
2. ANGIOTENSIN II: BINDS TO RECEPTORS, INCREASES SECTREION
PATHOLOGICAL CONDITION:
CUSHING SYNDROME; PROLONGED PLASMA GLUCOCORTICOID INCREASE
ACTH DEPENDENT OR INDEPENDENT
MINERALOCORTICOID:
1. ACTH: LARGER AMOUNT THAN FOR GLUCOCORTICOID NEEDED TO INCREASE SECRETION
2. ANGIOTENSIN II: PRIMARILY INCREASES SECRETION
3. RENIN-ANGIOTENSIN SYSTEM: INCREASES SECRETION
PATHOLOGICAL CONDITION:
GLUCOCORTICOID-REMEDIABLE ALDOSTERONSIM (GRA); AUTOSOMAL DISORDER WHERE
ACTH INCREASING ALDOSTERONE SECRETION IS NO LONGER TRANSIENT

 ADRENAL MEDULLA
 20% OF THE GLAND
 INNER LAYER
 A SYMPATHETIC GANGLION WHERE
POSTGANGLIONIC NEURONS LOST THEIR
AXONS AND BECAME SECRETORY
 CHROMAFFIN CELLS
 SECRETES; CATECHOLAMINES
EPINEPHRINE
NOR-EPINEPHRINE
DOPAMINE
 EMBRYONIC ORIGIN:
NEURAL CREST CELLS FROM ECTODERM
 BLOOD SUPPLY
PHRENIC AND RENAL ARTERIES

ADRENAL MEDULLARY HORMONES
CATECHOLAMINES
 ORGANIC COMPOUNDS
 SYNTHESIZED BY THE ADRENAL MEDULLA
 MONOAMINES WITH A CATECHOL (BENZENE WITH
2 HYDROXYL SIDE GROUPS) AND A SIDE CHAIN AMINE
 DERIVED FROM AMINO ACID TYROSINE
 WATER SOLUBLE, 50% BOUND TO PLASMA PROTEINS
 EPINEPHRINE, NOR-EPINEPHRINE, DOPAMINE
 EPINEPHRINE PRODUCED THE MOST
 NOR-EPINEPHRINE ALSO ENTERS THE CIRCULATION FROM
NORADREGENIC NERVE ENDINGS

BIOSYNTHESIS AND RELEASE OF CATECHOLAMINES
 FORMED BY HYDROXYLATION AND DECARBOXYLATION
OF THE AMINO ACID TYROSINE L-PHENYLALANINE
 TYROSINE IS CREATED FROM PHENYLALANINE BY HYDROXYL-
LATION BY THE ENZYME PHENYLALANINE HYDROXYLASE
 TYROSINE IS ALSO INGESTED FROM DIETARY PROTEIN
 PHENYLALANINE HYDROXYLASE IS FOUND IN THE LIVER
 TYROSINE INTO CATECHOLAMINES VIA A NA+ DEPENDENT CARRIER TYROSINE
 LATER CONVERTED TO DIHYDROXY-PHENYLALANINE (L-DOPA),
THEN CONVERTED INTO DOPAMINE BY CHROMAFFIN CELLS
BY TYROSINE HYDROXYLASE AND L-DOPA DECARBOXYLASE RESPECTIVELY
CATECHOL (BENZENE WITH 2 HYDROXYL SIDE
CHAINS)

 RATE LIMITING STEP IS CONVERSION OF TYROSINE TO L-DOPA
 AFTER SYNTHESIS OF DOPAMINE, TRANSPORTED TO VESICLE BY VMAT
 DOPAMINE IS THEN CONVERTED INTO NOREPINEPHRINE
BY DOPAMINE B-HYDROXYLASE
 (NOREPINEPHRINE IS SYNTHESISED IN THE VESICLE INSTEAD OF
BEING TRANSPORTED UNLIKE DOPAMINE)
 AFTER THIS, PHENYLETHANOLAMINE-N-METHYLTRANSFERASE (PMNT)
CATALYSES THE CONVERSION OF NOREPINEPHRINE TO EPINEPHRINE
 PNMT IS INDUCED BY GLUCOCORTICOIDS
 (NOREPINEPHRINE LEAVES THE VESICLE AND IS CONVERTED TO EPINEPHRINE)
 PHENYLKETONURIA EXCESS PHENYLALANINE

DOPAMINE
 CATECHOLAMINE SYNTHESIS STOPS AT DOPAMINE
 STORED IN SYNAPTIC CLEFT
 REUPTAKES VIA NA+ DEPENDENT DOPAMINE TRANSPORTER
 DOPAMINERGIC NEURONS IN BRAIN
o NIGROSTRIATAL SYSTEM
o MESOCORTICAL SYSTEM
 DOPAMINERGIC RECEPTORS LOSS BY AGE
 DOPAMINE RECEPTORS ARE METABOTROPIC
 SCHIZOPHRENIA
 RENAL VASODILATION

CATABOLISM OF CATECHOLAMINES
 NOREPINEPHRINE IS REMOVED FROM THE SYNAPTIC CLEFT BY BINDING TO POSTSYNAPTIC RECEPTORS, BINDING
TO PRESYNAPTIC RECEPTORS, REUPTAKE INTO THE PRESYNAPTIC NEURON OR CATABOLISM
 REUPTAKE VIA NET IS A MAJOR MECHANISM TO TERMINATE THE ACTIONS OF NOREPINEPHRINE.
 AFTER THE NORADREGENIC NEURONS ARE CUT, THEIR ENDINGS DENIGRATE WITH LOSS OF NET TO REMOVE
NOREPINEPHRINE FROM SYNAPTIC CLEFT.
 EPINEPHRINE AND NOREPINEPHRINE ARE METABOLISED TO BIOLOGICALLY INACTIVE PRODUCTS BY OXIDATION
AND METHYLATION. THE FORMER REACTION IS CATALYSED BY MONOAMINE OXIDASE (MAO) AND THE LATTER
BY CATECHOL-O-METHYLTRANSFERASE. MAO IS FOUND ON THE OUTER SURFACE OF MITOCHONDRIA.
 EXTRACELLULAR EPINEPHRINE AND NOREPINEPHRINE ARE FOR THE MOST PART O-METHYLATED. THE
RESPECTIVELY DERIVATIVES NORMETANEPHRINE AND METANEPHRINE IN URINE IS A GOOD INDEX OF RATE OF
SECRETION OF NOREPINEPHRINE AND EPINEPHRINE.
 SOME OF THE NOREPINEPHRINE IS CONSTANTLY BEING CONVERTED BY MAO INTO PHYSIOLOGICALLY INACTIVE
3, 4-DIHYDROXYMANDELIC ACID (DOMA) AND ITS CORRESPONDING GLYCOL (DHPG).

PHARMACOLOGY OF NORADREGINIC SYNAPSES
BIND TO ADRENORECPTORS AGONISTS AND ANTAGONISTS
 METYROSINE INHIBITS THYROSINE HYDROXYLASE
 RESPRINE BLOCKS VMAT
 BRETYLIUM AND GUNETHIDINE PREVENT EPINEPHRINE RELEASE
 COCAINE AND TRICYCLIC ANTIDEPRESSANT BLOCKS NET
 SYMPATHOMIMETICS MIMICS ACTION OF CATECHOLAMINES

Adrenal gland (Adrenal hormones and their production

DOSES
 NOREPINEPHRINE 300PG/ML
DURING ACTIVITY 1500PG/ML
 EPINEPHRINE 30PG/ML
DURING ACTIVITY 50PG/ML
 DOPMAINE 0.13PG/ML
 30UG OF NOREPINEPHRINE,
6UG OF EPINEPHRINE
700UG OF VMAT ARE EXCRETED IN 1 DAY
REGULATION
 STIMULI
 SLEEP
 ‘FIGHT OF FLIGHT’

Adrenal gland (Adrenal hormones and their production

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