Steroids of the 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+
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 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+
→ 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
