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SECRETION OF INDIVIDUAL STEROID HORMONES IS RESTRICTED TO SPECIFIC REGIONS OF THE ADRENAL CORTEX

GLOMERULOSA. CAPSULE. FASCICULATA. ALDOSTERONE. MEDULLA. RETICULARIS. ADRENAL CORTEX. RETICULARIS. CORTISOL. MEDULLA. MEDULLA. ANDROGENS. SECRETION OF INDIVIDUAL STEROID HORMONES IS RESTRICTED TO SPECIFIC REGIONS OF THE ADRENAL CORTEX. EPINEPHRINE NOREPINEPHRINE.

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SECRETION OF INDIVIDUAL STEROID HORMONES IS RESTRICTED TO SPECIFIC REGIONS OF THE ADRENAL CORTEX

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  1. GLOMERULOSA CAPSULE FASCICULATA ALDOSTERONE MEDULLA RETICULARIS ADRENAL CORTEX RETICULARIS CORTISOL MEDULLA MEDULLA ANDROGENS SECRETION OF INDIVIDUAL STEROID HORMONES IS RESTRICTED TO SPECIFIC REGIONS OF THE ADRENAL CORTEX EPINEPHRINE NOREPINEPHRINE

  2. STEROID SYNTHESIS ALL STEROIDOGENIC TISSUES CHOLESTEROL(C27) minusside chain + 20-keto GONADS - SIDE CHAIN PREGNENOLONE (C21) PREGNENOLONE(C21) DEHYDROEPIANDROSTERONE SULFATE (C19 :“DHEA-S”) + 3-keto + 17-OH desmolase sulfotransferase DEHYDROEPIANDROSTERONE” ’’DHEA” 17-OH PREGNENOLONE PROGESTERONE + 3-keto + 17-OH + 3-keto + 21-OH desmolase + 11-OH 17-OH PROGESTERONE ANDROSTENEDIONE(C19) 17-OH PREGNENOLONE CORTICOSTERONE + 21-OH TESTOSTERONE aromatase + 18-ALDEHYDE + 11-OH +3-keto ESTRONE aromatase ALDOSTERONE(C21) CORTISOL (C21) ADRENAL CORTEX DIHYDROTESTOSTERONE (C19) ESTRADIOL (C19)

  3. SYNTHESIS AND “SECRETION” OF STEROID HORMONES BY ADRENAL CORTEX 1 CHOLESTEROL IS TAKEN UP INTO MITOCHONDRIA EITHER DIRECTLY FROM PLASMA LDL/HDL OR FROM INTRACELLULAR CHOLESTEROL ESTERS “STORED” IN LIPID DROPLETS UPTAKE OF CHOLESTEROL ESTER FROM LDL AND HDL IN PLASMA KIDNEY StAR facilitates transfer of cholesterol molecules between inner and outer membranes ALDOSTERONE 2 Cholesterol in Intracellular Lipid droplets DIFFUSION OF STEROIDS OUT OF CELL P450scc StAR CORTISOL 4 P450c11 11-HYDROXYLASE 11-DEOXYCORTISOL ANDROGEN PRECURSORS REMOVAL OF SIDE CHAIN 17-OH PROGESTERONE ENDOPLASMIC RETICULUM OXIDATION OF STEROID NUCLEUS BY SPECIFIC P-450 HYDROXYLASES 5 - PREGNENOLONE (C21) GONADS 3

  4. 20 21 12 18 17 D 16 11 13 C 1 19 15 14 9 2 A 8 10 B 3 7 5 H H H C C C 3 3 3 C O C O 12 D 11 13 C A CHOLESTEROL  5-PREGNENOLONE 12 18 17 D 20,22-Desmolase P-450scc 16 11 13 C 1 19 15 14 4 6 9 A 8 2 10 DEHYDROGENASE B 7 3 5 6 4 17-OH PROGESTERONE C O 18 12 18 16 OH D 11 16 13 C 1 19 1 19 15 14 9 9 2 15 14 8 10 10 9 9 2 A 8 B 10 10 17-HYDROXYLASE B 7 5 7 O 5 O 6 6 PROGESTERONE 4

  5. ANDROSTENEDIONE ESTRONE O O 12 18 12 17 18 D D OH 11 16 11 13 13 C C 1 19 1 19 15 14 17 15 9 14 2 9 A 2 17 A 8 10 10 8 B B Aromatase 7 7 5 5 O HO 6 4 6 4 OH OH 12 12 18 17 18 D D 11 11 13 13 C C 1 19 1 19 15 15 14 14 9 9 2 A 2 A 8 10 10 8 B B 7 7 Aromatase 5 5 HO O 6 6 4 ESTRADIOL TESTOSTERONE DIHYDROTESTOSTERONE

  6. C O “PRE-RECEPTOR REGULATION” OF STEROID HORMONE ACTION 11ß-HYDROXYSTEROID DEHYDROGENASE - (11ß-HSD) 11ß- HSD TYPE 1 (LIVER) 11ß- HSD TYPE 2 (KIDNEY) 40 CORTISOL ACTIVE CORTISONE INACTIVE OH CH20H C O 12 18 12 18 O OH OH D OH D 16 11 13 16 11 11 13 C 1 19 1 19 15 14 9 9 15 14 9 2 A 9 2 A 8 10 10 8 10 10 B B B 3 3 3 7 3 7 5 5 O O 6 4 4 6

  7. LOCAL DEHYDROGENATION OF THE C11 HYDROXYL GROUP ON CORTISOL PROTECTS MINERALOCORTICOID RECEPTORS (MR) FROM INAPPROPRIATE ACTIVATION ALDOSTERONE:MR Kd~1nM CORTISOL or CORTISONE : MR Kd~1nM CORTISOL or CORTISONE : GR Kd~10nM IN SPITE OF THE HIGH AFFINITY OF CORTISOL / CORTISONE FOR THE MRINVITRO, GLUCOCORTICOIDS DONOT BIND TO MR IN TARGET TISSUES. THIS IS DUE TO THE “PRE-RECEPTOR INACTIVATION” OF CORTISOL BY 11ß-HSD2 CORTISOL CORTISOL LIVER ADIPOSE GONADS 11ß-HSD2 11ß-HSD1 OXIDATION OF C11 HYDROXYL CORTISOL CORTISONE GR MR KIDNEY,COLON SALIVARY GLAND, HEART nucleus RESPONSE NO RESPONSE nucleus

  8. BINDING AFFINITIES OF STEROIDS TO PLASMA PROTEINS SEX HORMONE BINDING GLOBULIN (SHBG) CORTISOL BINDING PROTEIN (CBP) ALBUMIN HORMONE CORTISOL 76 1.6 0.003 2.7 7.8 CORTISONE 0.005 ESTRADIOL 0.06 0.06 680 0.06 0.18 14 PREGNENOLONE 8.8 PROGESTERONE 0.06 24 17α -OH-PROGESTERONE 55 0.4 9.9 TESTOSTERONE 1600 0.04 5.3

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