LATE STEPS OF ALDOSTERONE BIOSYNTHESIS - SHEEP ARE NOT RATS

1. The last three steps of aldosterone biosynthesis have been demonstr ated to be catalysed by a single enzyme, referred to as CYP11B (or P45 0(11 beta)) in cow, pig, sheep and bullfrog and as CYP11B2 (or P450(al do)) in rat, human, mouse and hamster. 2. The related enzyme CYP11B1 ( also referred to as P450(11 beta)) in rat, human, mouse and hamster do es not have aldosterone synthesis activity, but no such enzyme has bee n reported in the cow, pig or sheep to date. 3. Exclusive aldosterone secretion in the zona glomerulosa (ZG) of the adrenal cortex in specie s such as rat, human, mouse and hamster could be ascribed to the restr icted distribution of CYP11B2 to the same region in the adrenal cortex . 4. In other species, such as cow, pig and sheep, the CYP11B enzyme i s expressed throughout the adrenal cortex and, thus, the exclusive ald osterone biosynthesis in the ZG could not be explained simply by the d istribution of the enzyme.5. We have shown in the sheep that potassium loading and acute sodium depletion stimulate the CYP11B transcript le vels, which are not further increased by chronic sodium depletion. 6. The predominant CYP11B in the sheep adrenal cortex catalyses the synth esis of aldosterone from deoxycorticosterone (DOC) in vitro, is expres sed throughout the adrenal cortex and the corresponding transcript lev els are increased by K+ loading or sodium depletion. In short, as far as the last step of aldosterone biosynthesis is concerned, sheep are d ifferent from rats. In the rat, the CYP11B2 transcript or protein is e levated by K+ loading or sodium depletion, but not the CYP11B1 transcr ipt or protein. 7. We propose that during severe sodium deficiency the re is a snitch in the aldosterone pathway to one preferentially involv ing 18-OH-DOC and not corticosterone.