Adrenal Gland Anatomy: Adrenal Cortex and Steroidogenic Pathways
- The three major secretory products of the adrenal cortex will be considered separately, but first the biosynthetic pathways for all steroid synthesis will be examined (figure). All adrenal steroids are derived from cholesterol by various modifications in its structure. Cholesterol can be synthesized by adrenal cells from acetyl CoA, but most is taken up from the blood by specific plasma membrane receptors that bind low density lipoproteins (LDL) that are rich in cholesterol.
- The rate-limiting step of steroid hormone biosynthesis is the conversion of the 27- carbon cholesterol molecule to the 21-carbon pregnenolone molecule via cleavage of the side chain between C20 and C22 by 20, 22 desmolase. This yields pregnenolone which is the common precursor of all steroids produced by the adrenals, gonads, and placenta. Which end product is ultimately secreted depends on the makeup of the particular cells involved. Glomerulosa cells lack 17 hydroxylase and thus follow the mineralocorticoid pathway (figure). They produce progesterone, deoxycorticosterone, corticosterone as intermediates to the final product, aldosterone. Cells of the fasciculata and reticularis follow the glucocorticoid pathway (figure) because they have 17 alpha hydroxylase and thus produce cortisol. Hydroxylation at the 17 position is also necessary for removal of the C17 side chain (C20 and C21) to convert 21-carbon steroids to 19- carbon steroids (figure). After C17 hydroxylation another desmolase, 17, 20 desmolase, may cleave the two carbon side chain producing the C19 structure. Hence, androgens can also be produced by these cells but not by glomerulosa cells. Biosynthesis of the various steroid hormones involves addition of functional groups to carbons 21, 17, 11, and 18 as shown in the figure. The reactions may take place in a different order than that presented and there may be additional minor products.
- These compounds are so similar in structure, yet exert such profoundly different effects, some knowledge of their structures is necessary to understand the patho-physiology caused by derange-ments in this system. Further treatment of steroidogenesis biochemistry will be found at the end of this chapter.