Endocrine Abstracts

The differences between the adrenocortical zones have attracted much attention.

There is considerable species variation, but the prevailing view is that each zone has steroidogenic activities, with varying specificity.Thus, the zona reticularis in the adult adrenal is thought to produce rather more C₁₉ steroids than the fasciculata, though this difference is not absolute. In most species, the greatest differences between the steroidogenic functions of the zones are between the glomerulosa and the fasciculata, and aldosterone is exclusively a glomerulosa product, whether there is one CYP11B species (as in the bovine) or two, as in the rat and human, in which CYP11B1 (11beta-hydroxylase) produces corticosterone or cortisol, whereas aldosterone synthase (CYP11B2) generates aldosterone (and 18-hydroxycorticosterone). The glomerulosa CYP11B2 products respond to angiotensin II, K⁺ ions and other factors, whereas the glucocorticoids, formed by CYP11B1 in the fasciculata/reticularis, respond to ACTH almost exclusively.

There are difficulties with this traditional interpretation. In the rat in particular, in situ hybridisation, immunocytochemistry and other data suggest that the glomerulosa is not a major site for de novo steroidogenesis, since it is poor in CYP11A (cholesterol side chain cleavage P-450), delta-5,3-beta-hydroxysteroid dehydrogenase, 21-hydroxylase and the essential cholesterol transporter, StAR. Indeed, in normal rat adrenals, CYP11B2 is itself confined to small clusters of cells only in the outermost glomerulosa cell layer. Accordingly, new interpretations are required, both of the mechanism for aldosterone synthesis, and of the biological significance of the major part of the glomerulosa that does not produce aldosterone. In addition, since it is likely that all of the cells of the cortex are derived from a stem cell source in the outermost part of the gland, mechanisms have to be sought for the abrupt change in phenotype of adrenocortical cells as they pass between the glomerulosa and fasciculata.

These concepts will be discussed.