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LCRS
YEAR 1 ENDOCRINOLOGY
The Adrenals and their hormones
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KIDNEY URETER
ADRENAL GLAND
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THE ADRENAL GLAND
ADRENAL MEDULLA
ADRENAL CORTEX
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
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ADRENAL CORTICAL ZONES
zona glomerulosazona fasciculata
zona reticularis
adrenal cortex
capsule Tributary
of central vein
medulla
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THE ADRENAL GLAND
ADRENAL MEDULLA
ADRENAL CORTEX
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
CATECHOLAMINES CORTICOSTEROIDS
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ADRENAL HORMONES
ADRENAL MEDULLA
(chromaffin cells)
CATECHOLAMINES
ADRENALINE (80%)
(epinephrine)
NORADRENALINE (20%)
(norepinephrine)
(DOPAMINE)
ADRENAL CORTEX
CORTICOSTEROIDS
MINERALOCORTICOIDS
Aldosterone
GLUCOCORTICOIDS Cortisol
SEX STEROIDS
Androgens, Oestrogens
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THE ADRENAL CORTEX
ZONA GLOMERULOSA
Aldosterone
ZONA FASCICULATA
ZONA RETICULARIS
Cortisol(Androgens, oestrogens)
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HO
CH3
CH3
CH3
CH CH2 CH2 CH2 C
CH3
CH3
H
CHOLESTEROL
GONADS
Progestogens(C21)
Androgens(C19)Oestrogens(C18)Mineralocorticoids(C21)
Glucocorticoids(C21)(Androgens)
ADRENALS
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1
2
34
56
7
8
9
10
11
12
13
14 15
16
1718
19
2021
Cyclopentanoperhydrophenanthrenecholesterol (c21)
progesterone 17a-hydroxyprogesterone
pregnenolone 17a-hydroxypregnenolone
deoxycorticosterone
corticosterone
aldosterone
11b-deoxycortisol
cortisol
dehydroepiandrosterone
androstenedione
MINERALOCORTICOID
GLUCOCORTICOID
ANDROGENS
(OESTROGENS)
P450scc
17a-hydroxylase 17a-hydroxylase
3b-hydroxysteroid
dehydrogenase
3b-hydroxysteroid
dehydrogenase
21 hydroxylase 21 hydroxylase
11b-hydroxylase 11b-hydroxylase
aldosterone
synthase
3b-hydroxysteroid
dehydrogenase
aromatase,
in peripheral tissues
17a-hydroxylase 17a-hydroxylase
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CORTICOSTEROID TRANSPORT
IN THE BLOOD
CORTISOL
75% bound to corticosteroid binding globulin(CBG, also known as TRANSCORTIN)
15% bound to albumin
10% free (unbound) bioactive
ALDOSTERONE
~60% bound to CBG
~40% free (unbound) bioactive
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CORTICOSTEROIDS IN
CIRCULATION
CORTISOL:
8am 140-690 nmol/l4pm 80-330 nmol/l
ALDOSTERONE:
upright 140-560 pmol/l
NOTE 1000-fo ld d ifference in concentrat ions
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ALDOSTERONE
stimulates Na+reabsorption in distal
convoluted tubule and cortical collectingduct (and in sweat glands, gastric
glands, colon)
stimulates K+
and H+
secretion, also indistal convoluted tubule and cortical
collecting duct
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ALDOSTERONE:
MECHANISM OF ACTION
PNa+
K+
H+ receptor
DNAnucleus
Distal convoluted tubuleTubular fluid ECF (blood)
mRNA
New proteins
ALDOSTERONE
Na+
Na+ Na+
K+
H+
EnzymesIon channelsTubule lumen
apical membrane
Blood
basolateral (serosal)
membranes
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THE JUXTAGLOMERULAR
APPARATUS
DISTAL TUBULE
Efferentarteriole
Afferentarteriole
GLOMERULUS
juxta-glomerular
cells
RENIN
Macula densa
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RENIN RELEASE
Decreased renal perfusion pressure(normally associated with decreased ABP)
Increased renal sympathetic activity (directto JGA cells)
Decreased Na+load to top of loop of Henle(macula densa cells)
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(CORTICOTROPHIN)
zonaglomerulosaof adrenalcortex
Na+K+LIVER
ANGIOTENSINOGEN
ANGIOTENSIN II
ACE
ANGIOTENSIN I
RENINenzyme
juxtaglomerular cellsof renal afferent arteriole
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
ALDOSTERONE
Other effects
e.g. vasoconstriction
CORTISOLS PHYSIOLOGICAL
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CORTISOLS PHYSIOLOGICAL
ACTIONS
NORMAL STRESS RESPONSE
SOME MINERALOCORTICOID EFFECTS
METABOLIC EFFECTS:
peripheral protein catabolismhepatic gluconeogenesis
increased blood [glucose]
fat metabolism
(lipolysis in adipose tissue) enhanced effects of glucagon
and catecholamines
RENAL AND CARDIOVASCULAR EFFECTS
e.g. excretion of water load
increased vascular permeability
other effects
e.g. on bone,
CNS, growth,
etc.
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EFFECTS OF LARGE
(PHARMACOLOGICAL)AMOUNTS OF
CORTISOL
ANTI-INFLAMMATORY ACTION
IMMUNOSUPPRESSIVE ACTION
ANTI-ALLERGIC ACTION
All associated with decreasedproduction of molecules such as
prostaglandins, leukotrienes, histamine,etc. as well as on the movement andfunction of leukocytes and theproduction of interleukins
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CORTICOSTEROID RECEPTORS
CORTISOL
GLUCOCORTICOID
RECEPTORS (GR)
ALDOSTERONE
ALDOSTERONE
RECEPTORS (MR)
CORTISONE
(INACTIVE)
11b-hydroxysteroid
dehydrogenase 2
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CORTISOL:
MECHANISM OF ACTION
receptor
DNAnucleus
mRNA
New proteinse.g. Annexin 1
Arachidonic acid
Prostaglandin synthesis
Annexin 1
receptor
OnNeighbouring
Cells?
CORTISOL
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ProOpioMelanoCorticotrophin
POMC
Pro-ACTH b-LPH
Pro-g-MSH ACTH g-LPH b-endorphin
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HYPOTHALAMUS
ADENOHYPOPHYSIS
(ANTERIOR PITUITARY)
STRESSORS BIOLOGICAL CLOCK(circadian rhythm)
ADRENAL
CORTEX
(zonae fasciculata
and reticularis)
feedbackloops
direct -ve
indirect -ve
CORTICOTROPHIN
(ACTH)
CRHVP
CORTISOL(and small amountsof androgens)
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CORTISOL:
CIRCADIAN RHYTHM
ACTH
CORTISOL
08.00 20.00 h
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DEHYDROEPIANDROSTERONE
(DHEA)
Precursor for androgens and oestrogens
Converted to active hormones within target
cells (which have the appropriate enzymes)
Peak serum levels at 20-30 years, then
decrease steadily with increasing age
Particularly important in postmenopausalwomen as precursor for oestrogen (and
androgen) synthesis by target tissues in the
absence of ovarian steroids