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