| page 219 |  | | page 220 |
| The cellular substructure of the adrenal cortex is arranged in three different layers. The inner two layers (zona fasciculata and zona reticularis) are responsible for the synthesis of cortisol, the main glucocorticoid, and the adrenal androgens. The outer layer (zona glomerulosa) is responsible for the synthesis of aldosterone, the main mineralocorticoid (see Chapter 19). Although many of the steps are similar, they are controlled by very different mechanisms and this has led to
the suggestion that the adrenal cortex may be considered as two separate endocrine organs.
|
| The biosynthesis of cortisol depends on stimulation by pituitary adrenocorticotropic hormone (ACTH) which binds to its plasma membrane receptor and triggers a range of intracellular events which cause hydrolysis of cholesterol esters stored in lipid droplets and activation of the cholesterol 20,22-desmolase enzyme. This is the rate-limiting step of steroidogenesis which converts C-27 cholesterol into pregnenolone, the first of the C-21 pregnane family of corticosteroids. Thereafter, conversion to cortisol requires a dehydrogenation-isomerization and three sequential hydroxylation reactions at C-17, -21, and -11 under the control of the CYP enzymes. Control of the rate of cortisol biosynthesis is achieved by negative feedback by cortisol on the secretion of ACTH (Chapter 37).
|
| The main stimulus to the synthesis of aldosterone is not ACTH but angiotensin II (see Chapter 22). Potassium is an important secondary stimulus. Angiotensin II, by binding to its receptor, and potassium, work cooperatively to activate the same first step in the pathway: the conversion of cholesterol into pregnenolone. The zona glomerulosa lacks the 17α-hydroxylase but has abundant amounts of 18-hydroxylase which is the first of a two-stage reaction, which yields the 18-aldehyde group found in aldosterone.
|
|
