F 16-5 Most corticosteroids have both –Mineralocorticoid and glucocorticoid activity –Different...

16. Adrenal gland16. Adrenal gland

V BS 122 2012

Luis A. Bate

Objectives

• To understand the structural relationships of the adrenal glands to its secretions

• To relate its function to stress• To understand its role in metabolism• To understand the consequences of

adrenal abnormal function

Adrenal gland

• Divided in capsule, cortex and medulla• CAPSULE

– Non-sectretory protective

• CORTEX– Zona glomerulosa mineralocorticoids– Zona fasciculata glucocorticoids and sex steroids– Zona reticularis glucocorticoids and sex steroids

• MEDULLA – Catecholamines, (epinephrine and norepinephrine)

F 16-1

ZONA GLOMERULOSA

ZONA FASCICULATA

ZONA RETICULARIS

MEDULLA

F 16-2

CRH

CRH

ACTH

TARGET

ACTHACTH

CORTICOTROPES

GLUCOCORTICOIDS

F 16-3

0 20 40 60 80

Mineralocorticoids

Glucocorticoids

Free

Albumin

CBG

Corticosteroid transport

• Most corticosteroids are bound to carrier proteins

F 16-4

Transport

• Carrier proteins fluctuate with physiological state– Estrogen in pregnancy increases CBG– Liver dysfunction reduces CBG

F 16-5

Corticosteroid function

• Most corticosteroids have both– Mineralocorticoid and glucocorticoid activity– Different potencies– Different concentrations

F 16-6

Mineralocorticoids

• Main representative is aldosterone (21C)

• Regulation of electrolyte balance– Absorption of Na+

– Secretion of K+

• Regulation of blood pressure

F 16-7

Angiotensinogen 453 aaAngiotensin I 10 aa

Angiotensin II 8 aa

Renin

Angiotensin-converting Enzyme

F 16-8

Angiotensinogen

Angiotensin I

Angiotensin II

Low BP

Na+ Retention

ALDOSTERONE PRODUCTIONALDOSTERONE PRODUCTION

F 16-9

Renal tubular cell

Na+

ALDOSTERONE ACTION

F 16-10

FILTRATE

Glucocorticoids

• Cortisol is the principal glucocorticoid in most domestic mammals

• Corticosterone is more important in avian, and murine species

• Equal role in cats and dogs

F 16-11

Glucocorticoids

• Main representatives are cortisol and corticosterone (21C)

• Important for directly or indirectly regulating metabolism

• Coping with stress• Anti-inflammatory

F 16-12

Metabolic effects of glucocorticoids

• Increases gluconeogenesis / glycogenesis (liver)

• Increases muscle catabolism• Increases liver protein synthesis• Reduce amino acid uptake and protein

synthesis (extrahepatic tissue)• Promotes mobilization of fatty acid

from adipose tissue• Enhances fatty acid oxidation in cells

F 16-13

Anti-inflamatory effects

• Stabilizing lysosomes– Lower proteolitic enzyme release

• Reduces capillary permeability– Prevents edema

• Impairs phagocytic activity and migration of white blood cells– Reducing production of PG and leukotrienes

• Immunosuppressant– Slowing proliferation of lymphocytes

• Anti-pyretic– Reduce interleukin-1 from white blood cells

F 16-14

PRNL

IACAAC

F 16-15

Catabolism

• Half life of glucocorticoids is about 60 minutes

• Some are structurally altered (saturate double bonds)

• Biologically inactive• Main catabolic pathway is conjugation

with sulfates and glucuronides– Usually in carbon 3

• Become water soluble (excreted in urine) F 16-16

Pathologies

• Hyperadrenocorticism (Cushing’s syndrome)

• Caused by:– Pituitary abnormality– Adrenal abnormality

F 16-17

Clinical signs

• Polydipsia• Polyurea• Polyphagia• Abdominal enlargement• Heat intolerance• Lethargy• Obesity• Muscle weakness

F 16-18

Abnormalities

• Hypoadrenalism (Addison’s Disease)– Deficiency in production of corticosteroids

• Mineralocorticoid deficiency– Decreased tubular sodium reabsorption– Loss of water– Plasma volume drops, cardiac volume

decreases

F 16-19

Abnormalities

• Glucocorticoid deficiency– Unable to maintain normal blood glucose– Causes weakness– Reduced infection fighting capabilities– Susceptible to stress

F 16-20

Catecholamines

• Synthesised as neurotransmitters throughout the body

• Produced as a hormone by the adrenal medulla

• Most important are:– Epinephrine (adrenalin)– Norepinephrine (noradrenalin)

F 16-21

Receptors for catecholamines

• Use four types of receptors • α control release from sympathetic

nerve endings– α1 postsynaptic terminals

– α2 presynaptic terminals

• β1 mainly in heart

• β2 smooth muscle

F 16-22

Metabolic effects of epinephrine

• Epinephrine more potent than norepinephrine on β2 receptors

• Similar effects than glucagon– Increases blood glucose– Increases liver glycogenolysis and

gluconeogenesis– Increases muscle glycogenolysis– Inhibits Insulin secretion– Stimulates glucagon secretion

F 16-23

Cont . . .

• Increases lipolysis rate on adipose tissue– Potentiated by glucocorticoids

F 16-23

α

α

1

2 β

P

AC

PK

Ca+

PLC

Ca+

EFFECT

F 16-24

β2

α 2

INCREASE INSULIN

DECREASE INSULIN

F 16-25

Summary of catecholamines effects in different tissues

β2

GLYCOGENOLYSIS

LIPOLYSIS

GLUCONEOGENESIS

F 16-26

β2

LIPOLYSIS

F 16-27

β2

GLYCOGENOLYSIS

F 16-28

Summary

• We have reviewed the relationship of the different zones of the adrenal gland and their secretions

• Associated adrenal function with stress• Reviewed the role of adrenal secretions on

metabolism• Discussed the most common

consequences of adrenal abnormal function

☺☻☺☻ Cheers

Done for now

© Luis A Bate 2012Luis A Bate

by Prepared for V BS 122

Adrenal gland

GENERAL ENDOCRINOLOGY