Steroids of Adrenal Cortex Flashcards
What are the steroids of the adrenal cortex
→ Glucocorticoids - cortisol
→ Mineralocorticoids - aldosterone
→ androgens
What does aldosterone do?
→ Maintains blood volume by regulating Na+
Where does the blood flow in the adrenal medulla?
→ Outer cortex to inner medulla
What does steroid hormone synthesis always start with?
→ Cholesterol
What does the cortex secrete?
→ Steroid hormones
What does the medulla secrete?
→ Adrenaline
What is the pathway in the zona glomerulosa?
Cholesterol ↓ Pregnenolone ↓ Progesterone ↓ Deoxycorticosterone ↓ Corticosterone ↓ Aldosterone
What is the zona fasciculata pathway?
Progesterone ↓ 17 OH progesterone ↓ Deoxycortisol ↓ Cortisol
What is the zona reticularis pathway?
Pregnenolone ↓ 17 OH pregnenolone ↓ DHEA ↓ Androstenedione
What is the function of mineralocorticoid?
→ Na+ retention
→ Active Na+ reabsorption
→ Active secretion of K+
What is the juxtaglomerular apparatus stimulated by?
→ Increased sympathetic activity
→ Decreased perfusion pressure
→ Decreased Na+ and Cl-
What stimulates aldosterone secretion?
→ K+
aldosterone secretion is NOT significantly affected by changes in plasma Na concentration
How does aldosterone work to retain Na+?
→ Increases Na+/K+/ATPase activity on the apical side
Why does cortisol not work in the kidney?
→ Cortisol levels are higher
→ Cortisol can stimulate the mineralocorticoid receptor
→ cortisol in the kidney gets converted to inactive cortisone
→ by 11 beta HSD 2
What is the syndrome of apparent mineralocorticoid excess?
→ Too much cortisol in the kidney
→ High BP
What family is the glucocorticoid receptor a part of?
→ Nuclear receptor super family
What are the 3 structural elements of the glucocorticoid receptor?
→ Ligand binding
→ DNA binding
→ N- terminal transcription co-factor binding
What do the glucocorticoid receptors do when the ligand binds?
→ Receptors dimerize
→ Translocate to nucleus
What is transactivation?
→ Glucocorticoid enhances transcription of the target gene
What is transrepression?
→ Glucocorticoid represses the transcription of the target gene
What are the functions of glucocorticoids?
→ Decreased glucose uptake → Increased proteolysis → Stimulates lipolysis → Gluconeogenesis → Maintaining glucose
What does hypocortisolism lead to?
→ hypotension
→ Inappropriate vasodilation
What are prostaglandins and leukotrienes derived from?
→ Lipid derived compounds
What is the first molecule to be synthesized in the inflammation pathway?
→ Arachidonic acid
What effect does cortisol have on the inflammation pathway?
→ Cortisol increases the expression of ANNEXIN - 1
→ Annexin 1 downregulates arachidonic acid
What is the pathway for the production of cortisol?
→ Hypothalamus makes CRH → CRH stimulates anterior pituitary → Anterior pituitary makes ACTH → ACTH stimulates the adrenal cortex → Adrenal cortex makes cortisol
What is primary adrenal insufficiency?
→ Addisons disease
What is secondary adrenal insufficiency?
→ Hypopituitarism
→ RAAS defect
→ Enzyme defect in steroid synthesis
What are the clinical features of Addisons?
→ Low adrenal steroids → high ACTH → Plasma Na+ - low → Plasma K+ - normal - high → high renin
When there is very low cortisol what two hormones are high?
→ ADH - plasma dilution so low Na+
cortisol inhibits ADH
→ ACTH
What is the ACTH receptor a part of?
→ Melanocortin group of receptors
Why does Addisons cause hyperpigmentation?
→ Excess circulating ACTH
→ Binds to melanocortin receptors
→ Pigmentation
What is Cushings disease due to?
→ Secondary
→ Increased ACTH due to pituitary adenoma
What is ACTH independent hypercortisolism?
→ Adrenal adenoma
→ Iatrogenic
What are clinical features of hypercortisolism?
→ Hypertension → Hyperglycaemia → truncal obesity → Fatigue, Muscle weakness → Virilization → Depression
What do low doses of dexamethasone usually do?
→ Suppress ACTH secretion via negative feedback
What suppresses ACTH secretion in Cushings and why?
→ a higher dose of dexamethesone
→ Pituitary cells have increased
→ more cortisol/dexamethesone is needed for a negative feedback
What happens if a high dose of dexamethesone does not suppress ACTH?
→ Ectopic source of ACTH
What effect does cortisol have on NO synthesis in the CVS?
have effect on NO synthesis so too much NO and inappropriate vasodilation.
What is the effect of glucocorticoids inhibit?
→inhibit the inflammatory response by inducing annexin-1 which inhibits phospholipase A2
→inhibits induction of COX
What happens when cortisol is very low?
CRH is high, and ADH rises and hyponatremia
Explain the rationale behind the low dose dexamethasone suppression test work
Dexamethasone: exogenous steroid. Act like cortisol
Low doses will normally supress ACTH secretion via negative feedback
How is ectopic ACTH linked with Cushing’s syndrome?
pituitary adenoma results in increased ACTH secretion, which drives excess cortisol production from adrenal cortex
Negative feedback loop is still intact, but greater mass of ACTH-secreting pituitary cells means set point is higher.
