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

2. STEROID SYNTHESIS GONADS ADRENAL CORTEX ALL STEROIDOGENIC TISSUES
CHOLESTEROL (C27)
+ 20-keto
minus side
chain
GONADS
- SIDE CHAIN
PREGNENOLONE (C21)
PREGNENOLONE (C21)
DEHYDROEPIANDROSTERONE SULFATE (C19 :“DHEA-S”)
+ 3-keto
+ 17-OH
desmolase
sulfotransferase
17-OH PREGNENOLONE
DEHYDROEPIANDROSTERONE” ’’DHEA”
PROGESTERONE
+ 21-OH
+ 17-OH
+ 3-keto
+ 3-keto
desmolase
+ 11-OH
17-OH PROGESTERONE
ANDROSTENEDIONE (C19)
17-OH PREGNENOLONE
CORTICOSTERONE
+ 21-OH
TESTOSTERONE
aromatase
+ 18-ALDEHYDE
+ 11-OH
+3-keto
ESTRONE
ALDOSTERONE (C21)
aromatase
need to add drawing of
follicle ( time for “round trip”)
passive diffusion into colloid space
CORTISOL (C21)
ADRENAL CORTEX
DIHYDROTESTOSTERONE (C19)
ESTRADIOL (C19)

3. SYNTHESIS AND “SECRETION” OF STEROID HORMONES BY ADRENAL CORTEX1
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
CO-0RDINATE
COLORS
p. 931/932
figS 51-2/ 51-3
SSBG AND CORTISOL-BINDING GLOBULIN
“ADRENOXIN”
ACTH STIMULATES WITHIN MINUTES due TO CHOLESTEROL
ALREADY PRESENT IN MITOCHONDRIAL INNER MEMRANE
KNOWN TO BE BLOCKED BY INHIBITOR OF PROTEIN SYNTHESIS
TRANSLOCATION OF STAR TO THE INNER MEMBRANE IS NOT REQUIRED
"STAR" IS NOT
REMOVAL OF
SIDE CHAIN
ANDROGEN
PRECURSORS
17-OH PROGESTERONE
ENDOPLASMIC RETICULUM
OXIDATION OF STEROID NUCLEUS
BY SPECIFIC P-450 HYDROXYLASES
5 - PREGNENOLONE (C21)
GONADS 3

4.  5-PREGNENOLONE CHOLESTEROL D C A B D C A B 17-OH PROGESTERONE D D C18 12 11 19 2 20 21 3 7 8 5 9 A 10 14 15 16 17 1 13
CHOLESTEROL
 5-PREGNENOLONE H 3 C C O 12 18 17
20,22-Desmolase
P-450scc D 16 11 13 C 1 19 4 6 9 14 15 A 2 10 8
DEHYDROGENASE B D C 12 11 A 13 O H 3 3 7 H 3 C 5 4 6
17-OH PROGESTERONE C O 18
Need to emphasize that steroids can move across membranes 12 18 D OH 16 11 16 13 C 1 19 1 19 9 9 14 15 2 9 9 14 15 10 10 8 2 A 10 10 8 B B
17-HYDROXYLASE 7 7 5 5 O O 6 4 6
PROGESTERONE

5. Martin Low: delta 5 pathway is favored ANDROSTENEDIONE ESTRONE D D C C12 18 17 12 18 D D OH 11 16 13 11 13 C C 1 19 1 19 14 15 17 2 9 14 15 A 10 8 2 9 A 17 10 8 B B
Aromatase 7 7 5 O 5 HO 4 6 6 4 OH OH 12 18 17 12 18 D D 11 11 13 13
Aromatase inhibitors/ tamoxifen/SERMS C
Martin Low:
delta 5
pathway is favored C 1 19 1 19 14 15 14 15 2 9 A 2 9 A 10 8 10 8 B B 7
Aromatase 7 5 O HO 5 6 4 6
ESTRADIOL
TESTOSTERONE
DIHYDROTESTOSTERONE

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

7. FROM INAPPROPRIATE ACTIVATION
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 MR IN VITRO, GLUCOCORTICOIDS DO NOT 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
RESPONSE
nucleus
NO RESPONSE
nucleus

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