Adrenal Hor m

8/10/2019 Adrenal Hor m

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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

Adrenal Hor m

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