LCRS

YEAR 1 ENDOCRINOLOGY
The Adrenals and their hormones

ADRENAL GLAND

KIDNEY

URETER

THE ADRENAL GLAND

ADRENAL MEDULLA

Zona Glomerulosa

Zona Fasciculata

Zona Reticularis
ADRENAL CORTEX

ADRENAL CORTICAL ZONES

adrenal cortex
zona glomerulosa
zona fasciculata

zona reticularis

capsule

Tributary
of central vein

medulla

THE ADRENAL GLAND

ADRENAL MEDULLA
Zona Glomerulosa

Zona Fasciculata

Zona Reticularis
ADRENAL CORTEX
CATECHOLAMINES

CORTICOSTEROIDS

ADRENAL HORMONES
ADRENAL MEDULLA
(chromaffin cells)

ADRENAL CORTEX
CORTICOSTEROIDS

CATECHOLAMINES
MINERALOCORTICOIDS
ADRENALINE (80%)
(epinephrine)
NORADRENALINE (20%)
(norepinephrine)
(DOPAMINE)

Aldosterone
GLUCOCORTICOIDS

Cortisol
SEX STEROIDS

Androgens, Oestrogens

THE ADRENAL CORTEX

ZONA GLOMERULOSA

Aldosterone
ZONA FASCICULATA

ZONA RETICULARIS

Cortisol
(Androgens, oestrogens)

CH3
H

C CH2 CH2 CH2 C

CH3

CH3

CHOLESTEROL

CH3

CH3

HO

GONADS

ADRENALS

Mineralocorticoids (C21)
Glucocorticoids (C21)
(Androgens)

Progestogens (C21)
Androgens (C19)
Oestrogens (C18)

20 21
12 18 17
11 13
16
14
15
19
1
9
2
10 8
Cyclopentanoperhydrophenanthrene

cholesterol (c21)

5
4

7
6

P450scc

17a-hydroxylase

pregnenolone
3b-hydroxysteroid
dehydrogenase

17a-hydroxylase

17a-hydroxypregnenolone
3b-hydroxysteroid
dehydrogenase

17a-hydroxylase

progesterone
21 hydroxylase

deoxycorticosterone
11b-hydroxylase

corticosterone
aldosterone
synthase

aldosterone
MINERALOCORTICOID

17a-hydroxyprogesterone

21 hydroxylase

dehydroepiandrosterone
3b-hydroxysteroid
dehydrogenase

17a-hydroxylase

androstenedione
aromatase,
in peripheral tissues

11b-deoxycortisol
11b-hydroxylase

cortisol
GLUCOCORTICOID

ANDROGENS
(OESTROGENS)

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

CORTICOSTEROIDS IN
CIRCULATION
CORTISOL:
8am
4pm
ALDOSTERONE:
upright

140-690 nmol/l
80-330 nmol/l
140-560 pmol/l

NOTE 1000-fold difference in concentrations

ALDOSTERONE
stimulates Na+ reabsorption in distal
convoluted tubule and cortical collecting
duct (and in sweat glands, gastric
glands, colon)
stimulates K+ and H+ secretion, also in
distal convoluted tubule and cortical
collecting duct

ALDOSTERONE:
MECHANISM OF ACTION
Tubular fluid

Distal convoluted tubule

Na+
Na+
Tubule lumen

Ion channels Enzymes

New proteins
K+

K+

Na+

ECF (blood)
Na+

Blood

mRNA
receptor

H+

ALDOSTERONE

H+
apical membrane

nucleus

DNA
basolateral (serosal)
membranes

THE JUXTAGLOMERULAR
APPARATUS
GLOMERULUS

Efferent
arteriole

RENIN

Afferent
arteriole

Macula densa
DISTAL TUBULE

juxta-glomerular
cells

RENIN RELEASE
Decreased renal perfusion pressure
(normally associated with decreased ABP)
Increased renal sympathetic activity (direct
to JGA cells)
Decreased Na+ load to top of loop of Henle
(macula densa cells)

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
LIVER

Other effects
(CORTICOTROPHIN)
e.g. vasoconstriction
K+

Na+

ANGIOTENSIN II
ACE
ANGIOTENSIN I

ANGIOTENSINOGEN

zona
glomerulosa
of adrenal
cortex

ALDOSTERONE
RENIN
enzyme
juxtaglomerular cells
of renal afferent arteriole

CORTISOLS PHYSIOLOGICAL
ACTIONS
NORMAL STRESS RESPONSE
METABOLIC EFFECTS:
peripheral protein catabolism
hepatic gluconeogenesis
increased blood [glucose]

fat metabolism
(lipolysis in adipose tissue)
enhanced effects of glucagon
and catecholamines

SOME MINERALOCORTICOID EFFECTS

RENAL AND CARDIOVASCULAR EFFECTS
e.g. excretion of water load
increased vascular permeability

other effects
e.g. on bone,
CNS, growth,
etc.

EFFECTS OF LARGE
(PHARMACOLOGICAL)AMOUNTS OF
CORTISOL

ANTI-INFLAMMATORY ACTION
IMMUNOSUPPRESSIVE ACTION
ANTI-ALLERGIC ACTION
All associated with decreased
production of molecules such as
prostaglandins, leukotrienes, histamine,
etc. as well as on the movement and
function of leukocytes and the
production of interleukins

CORTICOSTEROID RECEPTORS
CORTISOL

ALDOSTERONE
11b-hydroxysteroid
dehydrogenase 2

GLUCOCORTICOID
RECEPTORS (GR)

ALDOSTERONE
RECEPTORS (MR)

CORTISONE
(INACTIVE)

CORTISOL:
MECHANISM OF ACTION
Annexin 1
receptor

Arachidonic acid
Prostaglandin synthesis
e.g. Annexin 1
New proteins
mRNA
receptor

On
Neighbouring
Cells?

CORTISOL
nucleus

DNA

ProOpioMelanoCorticotrophin
POMC
b-LPH

Pro-ACTH

Pro-g-MSH

ACTH

g-LPH

b-endorphin

STRESSORS

BIOLOGICAL CLOCK
(circadian rhythm)

indirect -ve

HYPOTHALAMUS

CRH
direct -ve

VP
ADENOHYPOPHYSIS
(ANTERIOR PITUITARY)

CORTICOTROPHIN
(ACTH)
feedback
loops
CORTISOL
(and small amounts
of androgens)

ADRENAL
CORTEX
(zonae fasciculata
and reticularis)

CORTISOL:
CIRCADIAN RHYTHM

ACTH

CORTISOL

08.00

20.00

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 postmenopausal
women as precursor for oestrogen (and
androgen) synthesis by target tissues in the
absence of ovarian steroids