Cholesterol adrenocortical hormone precursor

Cholesterol is probably the best known steroid because of its association with atherosclerosis. However, biochemically it is also of significance because it is the precursor of a large number of equally important steroids that include the bile acids, adrenocortical hormones, sex hormones, D vitamins, cardiac glycosides, sitosterols of the plant kingdom, and some alkaloids. 

We first describe the biosynthesis of fatty acids, the primary components of both triacylglycerols and phospholipids, then examine the assembly of fatty acids into triacylglycerols and the simpler membrane phospholipids. Finally, we consider the synthesis of cholesterol, a component of some membranes and the precursor of steroids such as the bile acids, sex hormones, and adrenocortical hormones. 

P. is triosynthesized from cholesterol via pregnenolone. By conversion to 17a-hydroxyprogesterone, P. acts as a precursor of androgens and adrenocortical hormones. 

The suggestion that cholesterol might be the steroid precursor of the adrenocortical hormones has been confirmed by in vitro adrenal perfusion experiments using cholesterol-3-C. Again, as in the acetate experiments, the principal cortical constituents of the perfusates were compound F and corticosterone, both with significant radioactivity. - At the present time this transformation has been demonstrated only for adrenal perfusion, slices and homogenates being inactive for this purpose. 

The ubiquity of cholesterol in the animal body and its chemical similarity to the adrenocortical steroid hormones suggested that a product-precursor relationship might exist. This early suspicion was first confirmed by Bloch (1945) who showed that in man, deuterium labeled cholesterol could be converted to pregna-nediol, a known metabolite of progesterone. The direct conversion of cholesterol to progesterone and pregnenolone has been demonstrated (Hechter et al., 1951 Saba et al., 1954). 

The conversion of cholesterol-4-to corticosterone and cortisol has been achieved in perfused cow adrenal (Hechter et al., 1953) and a cell-free homogenate of cow adrenal cortex (Saba and Hechter, 1955). In man, administration of labeled cholesterol yields the characteristic urinary metabolites of cortisol (Wer-BiN and LeRoy, 1954, 1955). The conversion by human ovarian tissue of labeled acetate to progesterone (Sweat et al., 1960) and other hormones (Ryan and Smith, 1961) has also been reported. If cholesterol is indeed the precursor of the adrenocortical steroids, a predictable pattern of labeling should appear in hormones synthesized from labeled acetate. Caspi et al. (1956, 1957, 1962) have shown this to be the case. 

---