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