Glucocorticoids

Beta Switch Program

Beta Switch Program by Sue Heintze

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Cortisol is the primary glucocorticoid in man. It is synthesised from cholesterol in the zona fasciculata of the adrenal cortex. Synthesis of cortisol involves the

Zones of the adrenal cortex (85%)

Zona glomerulosa (15%): 21 carbon mineralocorticoids (aldosterone)

Zona fasciculata (70%): 21 carbon glucocorticoids (Cortisol, dehydroepiandrosterone

(DHEA)); and 17 and 18 carbon androgens Zona reticularis (15%): DHEA, an androgen precursor

Tyrosine d r l

Tyrosine hydroxylase ia

Dihydroxyphenylalanine (DOPA)

Aromatic L-amino acid decarboxylase Dihydroxyphenylethylamine (Dopamine)

Dopamine beta-hydroxylase Noradrenaline (dihydroxyphenylethanolamine) Phenylethanolamine N-methyl transferase Adrenaline

Figure 10.4 Pathway for catecholamine synthesis cytochrome P450 system. Secretion is episodic and variable, demonstrating a diurnal circadian rhythm. In the circulation, cortisol is largely bound to a specific glucocorticoid binding a2-globulin called corticosteroid-binding globulin, with the remainder being either bound to albumin (15%-20%), or unbound (5%). Stimuli to cortisol secretion include stress, hypoglycaemia, ACTH, haemorrhage.

The high-affinity glucocorticoid receptor in target cells is a 94 kDa single-chain polypeptide in the cytosol. After glucocorticoid binding, the hormone-receptor complex translocates to the nucleus and binds to DNA. Gene transcription is affected, stimulating the synthesis of specific proteins.

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