THE ADRENAL GLAND D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM

THE ADRENAL GLANDS zCORTEX: STEROID HORMONES SECRETED zMEDULLA: CATECHOLAMINES (EPINEPHRIN AND NOR- EPINEPHRIN) SECRETED. IT IS A MODIFIED SYMPATHETIC GANGLION

CORTEX: STEROID HORMONES SECRETED zMINERALOCORTICOIDS zGLUCOCORTICOIDS zSEX HOMONES

STEROID HORMONES zCHOLESTEROL IS A COMMON PRECURSOR zPREGNENOLONE IS A COMMON INTERMEDIATE zDERIVATIVES OF THE POLYCYCLIC PHENANTHRENE NUCLEUS

IMPORTANCE OF STEROID HORMONES: zREMOVAL OF CORTEX LEADS TO DEATH WITHIN 1 OR 2 WEEKS WITHOUT REPLACEMENT THERAPY zEVERY ORGAN SYSTEM IS AFFECTED

MINERALOCORTICOIDS zALDOSTERONE zELECTROLYTE BALANCE zBLOOD PRESSURE zRENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM zALDOSTERONE SECRETION REGULATED BY RENIN SECRETION IN THE KIDNEY VIA ANGIOTENSIN II zNEGATIVE FEEDBACK CONTROL VIA MONITORING BLOOD VOLUME

GLUCOCORTICOIDS zCORTISOL zGLOCONEOGENESIS zPERMISSIVE ACTIONS zSTRESS ADAPTATION zANTI-INFLAMITORY AND IMMUNOSUPPRESSANT zSEE TABLE I IN TEXT

PERMISSIVE ACTION OF CLUCOCORTICOIDS zSTRESS INCREASES OUTPUT OF ACTH FROM THE PITUITARY zTHESE HORMONES SEEM TO GOVERN PROCESSES FUNDAMENTAL TO NORMAL FUNCTION IN MOST CELLS zTREATED AN ADRENALECTOMIZED ANIMAL PERMITTED THE RESUMPTION OF THESE FUNCTIONS (HANS SELYE, 1930’S)

EFFECTS OF GLUCOCORTICOIDS ON ENERGY METABOLISM zMAINTAIN CARBOHYDRATE RESERVES zHYPOGLYCEMIA IF ABSENT zGLUCONEOGENESIS: DIRECT EFFECTS AND INCREASES IN ENZYMES zDECREASE UTILIZATION OF GLUCOSE BY MUSCLE AND ADIPOSE TISSUE AND LOWER SENSITIVITY TO INSULIN. DIABETES MAY ACCOMPANY CUSHING’S DISEASE WHICH IS A HYPERSECRETION

ANTI-INFLAMITORY EFFECTS OF GLUCOCORTICOIDS zINFLUENCE ON PROSTAGLANDINS: SUPPRESS SYNTHESIS OF CYCLO- OXYGENASE zPOSSIBLY INHIBIT HISTAMINE FORMATION zCYTOKINES (INTERLEUKIN-1)

GLUCOCORTICOIDS AND THE IMMUNE RESPONSE zBLOCK CYTOKINE PRODUCTION zMAY ALSO KILL T-CELLS

REGULATION OF CORTISOL SECRETION HYPOTHALAMUS CRH ANTERIOR PITUITARY ACTH ADRENAL CORTEX TARGET ORGANS CORTISOL STRESS DIURNAL RHYTHM INCREASED BLOOD GLUCOSE BLOOD AA BLOOD FATTY ACIDS

ACTION OF ACTH zSTIMULATES STEROIDOGENESIS zINCREASES STEROID SECRETION WITHIN 1 TO 2 MINUTES zPEAK RATES IN ABOUT 15 MINUTES zcAMP ---> PROTEIN KINASE A zABSENCE LEADS TO ATROPHY OF INNER ZONES OF ADRENAL CORTEX

SEX HOMONES zANDROGENS (TESTOSTERONE) zESTROGENS zLESS THAN GONADS

ADRENAL STEROID HORMONES IN THE BLOOD zBOUND TO TRANSCORTIN OR CORTICOSTEROID BINDING GLOBULIN (CBG) zSECRETED BY LIVER BUT AT 1/1000 TH THE CONCENTRATION OF ALBUMIN z95% CLUCOCORTICOIDS AND 65% ALDOSTERONE zLONG HALF LIFE (90 AND 30 MINUTES)

METABOLISM AND EXCRETION OF ADRENAL CORTICAL HORMONES zINACTIVATION MAINLY IN LIVER zMAKES THEM UNRECONIZABLE TO RECEPTORS zEXCRETED IN URINE

ADRENAL OVERSECRETION zMINERALCORTICOIDS: SODIUM RETENTION, POTASSIUM DEPLETION zCORTISOL:EXCESS GLUCONEOGENESIS- EXCESS GLUCOSE DEPOSITED AS FAT (CUSHING’S SYNDROME) zANDROGEN: MASCULINIZATION, PSEUDOHERMAPHODITISM, PRECOCIOUS PSEUDOPUBERTY, NO EFFECT IN ADULT MALES

ADRENAL INSUFFICIENY zCORTEX: ADDISON’S DISEASE zPOOR RESPONSE TO STRESS zLACK OF PERMISSIVE ACTION zPOTASSIUM RETENTION zHYPOTENSION

MEDULLA: CATECHOLAMINES zA MODIFIED SYMPATHETIC POST GANGLIONIC NEURON zEPINEPHRINE

ACTIONS OF EPINEPHRINE zMIMICS SYMPATHETIC NS zMOBILIZES STORED FAT AND CARBOHYDRATE zHEART AND BLOOD VESSELS

GENERAL ADAPTATION SYNDROME zFLIGHT OR FIGHT zEPINEPHRINE zCRH-ACTH-CORTISOL zRENIN-ANGIOTENSIN-ALDOSTERONE zVASOPRESSIN zCOORDINATED BY HYPOTHALAMUS zCAN BE INDUCED PSYCHOSOCIALLY

EPINEPHRINE, CORTISOL, AND GROWTH HORMONE zALL INCREASE BLOOD GLUCOSE AND FATTY ACIDS zCORTISOL INCREASES BLOOD AA AND DECREASES MUSCLE PROTEIN zGH DECREASES BLOOD AA AND INCREASES MUSCLE PROTEIN