ADRENAL CORTEX Introduction Adrenal Location Superior Pole of

ADRENAL CORTEX

Introduction • Adrenal Location – Superior Pole of each Kidney – Retroperitoneal – Embedded in the Perirenal fat pad. – Left gland sits slightly more superior than right gland

Adrenal Gland • Adrenal Cortex • Adrenal Medulla/ Chromaffin Tissue • Different embryological origins • Not together below birds

Adrenal Cortex • Embryology – Intermediate Mesoderm • Zones – Zona Glomerulosa – Zona Fasciculata – Zona Reticularis Medulla

Adrenal Cortex Cytology • Lipid Inclusions • Well Developed SER • Mitochondria with Tubular Cristae • Capillary Adjacent to each Cell

Cholesterol Side Chain • LDL • De Novo Synthesis

Mineralocorticoids Side-Chain Cleavage 3 -OH dehydrogenase Steroid Pathways Gluco. Androgens corticoids Estrogen Aromatase 21 -hydroxylase 11 -hydroxylase 18 -OH steroid dehydrog. 17 -OH Steroid Dehydrogenase 17 -OHase C 17 -20 Lyase 16 -OHase

Mineralocorticoids

Mineralocorticoids Side-Chain Cleavage 3 -OH dehydrogenase Z. Glomerulosa Gluco. Androgens corticoids Estrogen Aromatase 21 -hydroxylase 11 -hydroxylase 18 -OH steroid dehydrog. 17 -OH Steroid Dehydrogenase 17 -OHase C 17 -20 Lyase 16 -OHase

Mineralocorticoids • • C-21 Steroids Primarily produced by zona glomerulosa Principal mineralocorticoid is aldosterone Aldosterone actions – Promote Na+ reabsorption – Inhibit K+ reabsorption – Antidiuretic – Acts primarily on the cortical collecting duct & DCT

Regulation of Aldosterone Secretion Na+ K+ Na+ K+ Z. Glomerulosa Aldosterone Na+ Reabsorption Kidney K+ Reabsorption

Regulation of Aldosterone Secretion Angiotensinogen Kidney Juxtaglomerular Renin Cells Blood Pressure Angiotensin-I Blood Volume Water Reabsorption Na+ Reabsorption Kidney Lung Converting Enzyme Angiotensin-II Aldosterone Z. Glomerulosa

Regulation of Aldosterone Secretion Hypothalamus CRH Anterior Pituitary ACTH Z. Glomerulosa Aldosterone

Atrial Natriuretic Hormone • 28 amino acid peptide • Similar peptides produced in other organs • Actions – c. GMP is second messenger – Increases GFR – Inhibits Na+ and water reabsorption

Regulation of ANH Venous Return Atrial Stretch Receptors ANH Blood Volume Kidney Water Reabsorption Na+ Reabsorption

Glucocorticoids

Mineralocorticoids Side-Chain Cleavage 3 -OH dehydrogenase Z. Fasiculata Gluco. Androgens corticoids Estrogen Aromatase 21 -hydroxylase 11 -hydroxylase 18 -OH steroid dehydrog. 17 -OH Steroid Dehydrogenase 17 -OHase C 17 -20 Lyase 16 -OHase

Which ones are glucocorticoids? • • Cortisol 11 -deoxycorticosterone 17 -hydroxyprogesterone 17 -hydroxypregnenolone • Cortisol Most Potent • 11 -deoxycorticosterone, very weak, but does act as feedback effector and has potent mineralocorticoid activity. • Remainder are inactive

Serum binding proteins • Corticosteroid binding globulin (CBG) – 75% of Cortisol bound to CBG – 10% of Aldosterone bound to CBG • Albumin – 15% of Cortisol bound to Albumin – 50% of Aldosterone bound to Albumin • Free – 10 % of Cortisol – 40 % of Aldosterone

Actions of the Glucocorticoids

Anti-inflammatory • Inhibit Prostaglandin production – Inhibit phospholipase A 2 • Inhibit secretion of Interleukin-I • Prevents movement of PMNs, lymphocytes, & monocytes from blood into areas of injury. • Decrease lymphocyte production

Intermediary Metabolism • • • Stimulates gluconeogenesis Protein catabolic Decrease glucose catabolism Increase lipolysis Inhibit DNA synthesis.

Growth • Glucocorticoids inhibit mitosis • Inhibit bone formation and mineralization – Decrease intestinal absorption of Ca++ – Stimulates PTH (secondarily)

Connective Tissues • Inhibit collagen formation • Decreased bone deposition

Blood • Increased intravascular levels of neutrophils • Decreased intravascular levels of lymphocytes, monocytes, & eosinophils • Diminished immune response

Cardiovascular • Increase blood pressure – Increased cardiac output – Increased vascular tone – Possibly augmenting action of catecholamines – Increasing number of adrenergic receptors

Effects on CNS • Easily enter Brain • Neurons have glucocorticoid receptors • Physiologic effect unknown • Excess or deficiency of glucocorticoids known to profoundly alter behavior and cognitive function.

Effects on Other Hormones • Inhibit TSH production • Inhibit Gn. RH production

Ulcer formation • Inhibit Prostaglandin production • Immunosuppression

ACTH Side-Chain Cleavage 3 -OH dehydrogenase Mineralocorticoids Z. Fasiculata Gluco. Androgens corticoids Estrogen Aromatase 21 -hydroxylase 11 -hydroxylase 18 -OH steroid dehydrog. 17 -OH Steroid Dehydrogenase 17 -OHase C 17 -20 Lyase 16 -OHase

Regulation of Glucocorticoid Secretion STRESS Circadian Rhythm Hypothalamus CRH Anterior Pituitary ACTH Z. Fasciculata & Reticularis Cortisol

General Adaptation Syndrome (Selye) Cortisol STRESS • Alarm • Resistance • Exhaustion---Death Time

Adrenal Androgens • Dehydroepiandrosterone (DHEA) – DHEA-S • Androstenedione

Fetal Adrenal Cortex • Develops first in fetal adrenal gland • Produces androgens (DHEA) • Replaced by definitive cortex

Pathologies of the Adrenal Cortex

Adrenocortical Insufficiency (Addison’s Disease) • Signs & symptoms – Weakness, Fatigue – Anorexia, Weight loss – Hyperpigmentation (primary only) – Hypotension – G-I disturbances – Salt craving • Crisis • Treatment

Hypersecretion (Cushing’s Disease) • Primary, secondary, or tertiary • Ectopic ACTH production • Signs and symptoms – Obesity – Thinning of the skin – Striae – Hirsutism – Hypertension

Hypersecretion (Cushing’s Disease) – Weakness – Gonadal dysfunction – Glucose intolerance • Treatment

Androgenital syndrome • Excess adrenal androgen production. • Maybe due to tumor

Enzyme Deficiencies Side-Chain Cleavage 3 -OH dehydrogenase 21 -Hydroxylase Deficiency 21 -hydroxylase 17 -OHase C 17 -20 Lyase

Enzyme Deficiencies Side-Chain Cleavage 3 -OH dehydrogenase 11 -Hydroxylase Deficiency 21 -hydroxylase 11 -hydroxylase 17 -OHase C 17 -20 Lyase

Enzyme Deficiencies Side-Chain Cleavage 3 -OH dehydrogenase 3 -Hydroxysteroid Dehydrogenase Deficiency 17 -OHase C 17 -20 Lyase