CORTICOSTEROIDS
Overview
- corticosteroids are steroid hormones synthesized and secreted by the adrenal cortex
- the adrenal cortex consists of 3 layers (listed from outermost to innermost)
LAYER DESCRIPTION
ZONA GLOMERULOSA - synthesize mineralocorticoids (primarily aldosterone)
ZONA FASCICULATA - synthesize glucocorticoids (primarily hydrocortisone
(“cortisol”))
ZONA RETICULARIS - synthesize and store sex hormones (primarily testosterone and oestradiol)
- all the corticosteroids are steroid hormones synthesized from cholesterol in a complex meshwork
MINERALOCORTICOIDS GLUCOCORTICOIDS 
SEX HORMONES
SEX HORMONES
CHOLESTEROL 
PREGNONELONE 
3-dehydrogenase 17-HYDROXYPREGNONELONE 
→ DEHYDROEPIANDROSTERONE 
3dehydrogenas
PROGESTERONE 
17-HYDROXYPROGESTERONE 21-hydroxylase ANDROSTENEDIONE
↓17-dehydrogenase
11-DEOXYCORTICOSTERONE 11-DEOXYCORTISOL TESTOSTERONE
aromatase 
11- hydroxylase OESTRADIOL
HYDROCORTISONE
OESTRIOL
CORTICOSTERONEALDOSTERONE OESTRONE
MINERALOCORTICOIDS GLUCOCORTICOIDS SEX HORMONES
SEX HORMONES CHOLESTEROL
PREGNONELONE 3-dehydrogenase 17-HYDROXYPREGNONELONE → DEHYDROEPIANDROSTERONE 3dehydrogenas
PROGESTERONE 17-HYDROXYPROGESTERONE 21-hydroxylase ANDROSTENEDIONE
↓17-dehydrogenase
11-DEOXYCORTICOSTERONE 11-DEOXYCORTISOL TESTOSTERONE
aromatase 11- hydroxylase OESTRADIOL HYDROCORTISONE
OESTRIOL
CORTICOSTERONEALDOSTERONE OESTRONE
MINERALOCORTICOIDS GLUCOCORTICOIDS SEX HORMONES
SEX HORMONESCHOLESTEROL PREGNONELONE 3-dehydrogenase 17-HYDROXYPREGNONELONE → DEHYDROEPIANDROSTERONE
→ DEHYDROEPIANDROSTERONE 3dehydrogenas
PROGESTERONE 17-HYDROXYPROGESTERONE 21-hydroxylase ANDROSTENEDIONE
↓17-dehydrogenase
11-DEOXYCORTICOSTERONE 11-DEOXYCORTISOL TESTOSTERONE
aromatase 11- hydroxylase OESTRADIOL HYDROCORTISONE
OESTRIOL
CORTICOSTERONEALDOSTERONE OESTRONE
- though this meshwork might seem overly complex to memorize, please notice that the enzymes in each row (see above) essentially are the same (!)
MINERALOCORTICOIDS
Overview
- mineralocorticoids are synthesized by the zona glomerulosa of the adrenal cortex
- the main mineralocorticoid is aldosterone
- aldosterone acts on aldosterone receptors exclusively found in the late distal tubule of the kidney nephrons
- consequences of aldosterone stimulation, see 24
- regulation of aldosterone secretion is done by the renin angiotensin aldosterone system
Relevant Drugs
- 3 groups
1) ALDOSTERONE RECEPTOR AGONISTS
- aldosterone receptor agonists agonizes aldosterone receptors, thus causing
increased water/sodium retention and increased potassium/hydrogen ion excretion
- 2 types
DRUG NAME DESCRIPTION ALDOSTERONE General information
- not used clinically
FLUDROCORTISONE General information
- administered orally
Medical uses
- treatment of hypoadrenocorticism
(“addison’s disease”)
2) ALDOSTERONE RECEPTOR ANTAGONISTS
- “potassium-sparing diuretics”
- aldosterone receptor antagonists antagonize the action of aldosterone on
aldosterone receptors, thus causing decreased water/sodium retention and decreased potassium/hydrogen ion excretion
3) CORTICOSTEROID SYNTHESIS INHIBITORS
- corticosteroid synthesis inhibitors inhibit enzymes responsible corticosteroid synthesis (see above), thus causing decreased synthesis of aldosterone, hydrocortisone and sex hormones
- 2 types
DRUG NAME DESCRIPTION TRILOSTANE General information
- 3-dehydrogenase inhibitor
Medical uses
- treatment of hyperaldosteronism (“cushing’s syndrome”)
- treatment of hypercortisolism (“conn’s syndrome”)
METYRAPONE General information
- 11-hydroxylase inhibitor
- same as trilostane (see above)
GLUCOCORTICOIDS
Overview
- glucocorticoids are synthesized by the zona fasciculata of the adrenal cortex
- the main glucocorticoid is hydrocortisone (“cortisol”)
- hydrocortisone acts on glucocorticoid receptors found in most cells
- hydrocortisone also has a strong action on aldosterone receptors (see above)
- consequences of hydrocortisone stimulation include
CONSEQUENCE DESCRIPTION CARBOHYDRATE METABOLISM - decreased glucose uptake
- decreased glycolysis
- increased gluconeogenesis
FAT METABOLISM - increased deliberation of free fatty acids from adipose tissue
- increased beta-oxidation
PROTEIN METABOLISM - decreased protein uptake
- decreased protein synthesis
- increased protein catabolism
CALCIUM HOMEOSTASIS - decreased calcium absorption from the GI
tract
- decreased osteoblast activity
- increased osteoclast activity
- increased calcium excretion by the kidneys
IMMUNE DEFENSE SYSTEM - decreased synthesis of COX-2 (see 51/52)
- decreased synthesis of eicosanoids (due to decreased COX-2 synthesis)
- decreased edema, pain and fever (due to decreased eicosanoid synthesis)
- decreased synthesis of nitric oxide synthase
- decreased vasodilation (due to decreased nitric oxide synthase synthesis)
- decreased synthesis of GM-CSF
- decreased proliferation of granulocytes and monocytes/macrophages in the bone marrow (due to decreased GM-CSF synthesis)
- decreased synthesis of TNF-gamma
- decreased synthesis of VCAM-1 and ICAM-1 cell adhesion molecules (due to decreased
TNF-gamma synthesis)
- decreased migration of granulocytes and monocytes/macrophages (due to decreased VCAM-1/ICAM-1 synthesis)
- decreased activation of helper T-cells
- decreased secretion of IL-2 from helper T- cells (due to decreased activation of T-helper cells)
- decreased activation of cytotoxic T-cells (due to decreased IL-2 secretion from helper T- cells)
- decreased activation of fibroblasts
- decreased deposition of collagen and glycosaminoglycans (due to decreased activation of fiboblasts)
- decreased wound healing and fibrosis (due to decreased deposition of collagen/glycosaminoglycans)
- decreased activation of mast cells
- decreased secretion of histamine (due to decreased activation of mast cells)
- decreased bronchoconstriction (due to decreased histamine release)
- decreased synthesis of complement factors by the liver
- regulation of hydrocortisone secretion is done by ACTH (see 54)
- 12 -
Relevant Drugs
- 1 group
1) GLUCOCORTICOID RECEPTOR AGONISTS
- 6 types
DRUG NAME DESCRIPTION HYDROCORTISONE General information
- cortisol itself
- administered orally, IV, intramuscularly,
intra-articularly, by inhalation, and/or dermally
Medical uses
- treatment of adrenal hypofunction
(“addison’s disease”)
Side effects
- cushing’s syndrome-like syndrome (due to negative feedback on the anterior lobe of the pituitary gland, see 54)
- hyperglycemia (due to altered carbohydrate metabolism)
- diabetes (due to hyperglycemia)
- inhibition of growth in children (due to
altered protein metabolism and altered calcium homeostasis)
- osteoporosis in adults (due to altered calcium homeostasis)
- increased susceptibility to infections (due to immunosuppression)
- generalized edema (due to sodium/water retention by action on aldosterone receptors)
- adrenal hypofunction (if withdrawn rapidly)
CORTISONE General information
- pro-drug
- activated to hydrocortisone in the body
- same as hydrocortisone (see above)
Medical uses
- treatment of adrenal hypofunction
(“addison’s disease”)
- treatment of inflammations (including exophthalmus of hyperthyroidism)
- treatment of hypersensitivity reactions
(including asthma)
Side effects
- same as hydrocortisone (see above)
PREDNISOLONE General information
- synthetic hydrocortisone derivative
- same as hydrocortisone (see above)
Medical uses
- treatment of inflammations
- treatment of hypersensitivity reactions
(including asthma)
Side effects
- same as hydrocortisone (see above)
PREDNISONE General information
- pro-drug
- activated to prednisolone in the body
- same as prednisolone (see above)
BETAMETHASONE General information
- same as prednisolone (see above)
DEXAMETHASONE General information
same as prednisolone (see above)
SEX HORMONES
Overview
- sex hormones are synthesized by the zona reticularis of the adrenal cortex
- the main sex hormones of the zona reticularis are testosterone and oestrogens
- however, the zona reticularis only maintains a basal level of testosterone and oestrogens in
childhood and menopause, with the gonads synthesizing the bulk of the testosterone and oestrogens in puberty and adulthood (see 56/57/58)
- regulation of sex hormone secretion by the zona reticularis is done by ACTH
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