ENDOCRINOLOGY
ADRENAL CORTEX
DR SYED SHAHID HABIB
MBBS FCPS DSDM
CORTEX
ZONAGLOMERULO
SA
MINERALOCORTICOIDS (ALDOSTERONE)
ZONAFASICULATA
GLUCOCORTICOIDS (CORTISOL)
PREDOMINANTLY
ZONARETICULARIS
ANDROGENS (DEHYDROEPIANDROSTE
RONE)PREDOMINANTLY
MEDULLACATECHOLAMINES (EPINEPHRINE AND NOREPINEPHRINE)
Class of SteroidMajor
RepresentativePhysiologic Effects
Mineralocorticoids AldosteroneNa+, K+ and water
homeostasis
Glucocorticoids CortisolGlucose
homeostasis and many others
AndrogensDehydroepiand
rosteroneAndrogenic
Activity
TWO TO THREE DOZEN
• Source Primarily zona fasiculata• Chemistry C21 Cortico Steroid• Half Life 60-90 min• Fate Conjugated in Liver and then Excreted in urine or bile. • Transport Only about 10% free & 90 % bound to corticosteroid-binding globulin (transcortin)
Cortisol
MECHANISM OF ACTION
R
Transformation of Receptor to expose
DNA binding Domain
Binding to Enhancer like Segment in DNA
Pre mRNA
mRNA
mRNA
Protein
R
EFFECTS
PHYSIOLOGIC EFFECTS OF GLUCOCORTICOIDS
EFFECTS ON INTERMEDIARY METABOLISM
CARBOHYDRATES
FATS
PROTEINS
PHYSIOLOGIC EFFECTS OF GLUCOCORTICOIDS
EFFECTS ON METABOLISM
• Catabolic proteolytic action: Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis
• Gluconeogenesis, Glycogenesis and Anti Insulin Action Inhibition of glucose uptake in muscle and adipose tissue
• Lipolytic Action Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle
EFFECTS ON INFLAMMATION AND IMMUNE FUNCTION
• Glucocorticoids have potent anti-inflammatory and immunosuppressive properties.
PHYSIOLOGIC EFFECTS OF GLUCOCORTICOIDS
OTHER EFFECTS OF GLUCOCORTICOIDS• Glucocorticoids have multiple effects on FETAL
DEVELOPMENT (maturation of the lung and production of the surfactant necessary for extrauterine lung function)
Physiologic Effect Clinical expressionCortisol Deficiency
Cortisol exces
CARBOHYDRATE METABOLISM• Increased gluconeogenesis• Decreased glucose utilization
Hypoglycemia hyperglycemia
• Decreased sensitivity to insulin
Increased Insulin sensitivity
Insulin resistance
PROTEIN METABOLISM• Decreased extrahepatic
amino acid utilization • Increased gluconeogenesis
Hypoglycemia Dec protein in bone, skin, muscle
Poor wound healing
FAT METABOLISM• Increased lipolysis, decreased
lipogenisis Weight loss Hyperlipemia
• Distribution of fat Truncal obesity
DIURNAL VARIATION
CORTISOL
CRH
ACTH
PhysicalStress
Mental stress
LIVERFATS
MUSCLEBLOOD CELLS
-
-
+
+
Phlebotomist
FEEDBACK CONTROL
OF CORTSOLSECRETION
Trauma Pain
Emotion
CUSHING’S SYNDROME
ALDOSTERONE
• Source Zona Glomerulosa• Chemistry Steroid• Half Life 20 min• Fate Conjugated in Liver and then Excreted in urine or bile. • Transport Only about 40% free & 60 % bound to Albumin
WHAT ARE THE TARGETS OF ALDOSTERONE?
ALDOSTERONE TARGETS
Renal tubules
Sweat Glands
Salivary glands
Gastrointestinal Tract
Increases Na Epithelial channels
Effect Of Aldosterone On Cortical Collecting Duct
MECHANISM OF ACTION
R
Transformation of Receptor to expose
DNA binding Domain
Binding to Enhancer like Segment in DNA
Pre mRNA
mRNA
mRNA
Protein
ENaCs
Na K Adenosine Triphosphatase
Ushu
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