The Adrenal Functional Unit: A Hypothesis

Abstract

THE ADRENAL FUNCTIONAL UNIT: A HYPOTHESIS* ANDRES CARBALLEIRA and LAWRENCE M. FISHMANt The secretory products of the endocrine glands fall into two general categories of chemical substances: nitrogen-containing hormones, consisting of polypeptides (insulin, ACTH) or substituted amino acids (thyroxine, epinephrine); and steroid hormones, tetracyclic lipids derived from a common precursor (cholesterol), that can be classified according to their biological properties as glucocorticoids, mineralocorticoids , or sex hormones. The nitrogen-containing hormones are elaborated by cells derived from the ectoderm (pituitary, adrenal medulla) or the endoderm (thyroid, pancreas), while steroid hormones are secreted only by cells of mesodermal origin (testis, ovary, adrenal cortex) [I]. The adrenal gland, as a consequence of its compound structure of mixed germ layer derivation, represents the unique circumstance of the secretory confluence ofboth nitrogen-containing and steroid hormones from a single organ. In the mammalian adrenal gland, within the confines of a common capsule is found a central zone (the adrenal medulla) derived from the ectodermal neural crest and elaborating nitrogen-containing hormones (catecholamines), surrounded by a peripheral zone (the adrenal cortex) that develops from the mesodermal coelemic epithelium and synthesizes steroid hormones. Not only are these two endocrine tissues of diverse origin in unique topographic juxtaposition, but also their vascular relationships are such that the secretory products of the cortex perfuse the medulla through a rich portal network. Furthermore, the exposure of medullary cells to cortical metabolites may be altered by the action of sphincter-like muscle bundles in the central adrenal vein, the common *This hypothesis is dedicated to Dr. J. S. L. Browne, professor of investigative medicine emeritus, McGiIl University, under whose guidance A. C. began his studies of the relationship between adrenal cortex and medulla. The authors warmly acknowledge the contributions of Drs. Eleanor H. Venning, John C. Beck, and Afzal Z. Mehdi to the early phases of experimental work from which this formulation evolved. fResearch Service, Veterans Administration Medical Center, 1201 NW 16 Street, Miami, Florida 33125, and Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101.© 1980 by The University of Chicago. 0031-5982/80/2304-0203$01.00 Perspectives in Biology and Medicine ¦ Summer 1980 | 573 outflow channel for both tissues [2]. The cortex and the medulla thus constitute a clearly interrelated anatomical unit. This concentric arrangement of adrenal cortex and medulla is found only in eutherian mammals among vertebrate classes. Varying degrees of intermingling of the analogues of cortex (interrenal gland) and medulla (chromaffin cell aggregates) are evident starting with prototheria , however, and continuing in birds, reptiles, and amphibians. Intertwining of these two cell populations prevails also in most fishes, with the exception of very primitive orders (cyclostomes, chondrichthyes ) in which separate conglomerates ofthe cortical analogue and of chromaffin cells are found in close relation to the posterior cardinal veins or distributed metamerically along the kidney [3]. Not surprisingly, transitional phases in the ontogenic development of the human adrenal gland mirror the morphological relationships found during the phylogenetic evolution of its steroid- and catecholamineproducing components [4]. In the early stages of embryonic growth, the immature cortical cells are severed from the mesodermal corticogonadal anlagen, coalesce into compact masses on either side of the aorta, and are, at this stage, completely isolated from the islets of immature chromaffin cells that have detached themselves from the sympathetic primordia. As embryogenesis proceeds, some chromaffin cells migrate toward the cortical buds, penetrating them in cordlike fashion until finally the pheochromoblasts begin to coalesce centripetally. The development of the human adrenal gland is, however, far from complete at birth, and shortly after delivery the gland undergoes a regressive change characterized by the precipitous degeneration of the innermost section of the cortex, the so-called X or fetal zone, which is highly active in steroid biosynthesis during intrauterine life. Cells spared from this process eventually proliferate, giving rise to the zona reticularis , while the rapidly growing outer strata of the cortex arrange themselves into the definitive zona fasciculata and zona glomerulosa. The development of medullary cells takes place at a much slower tempo, and they attain their intense chromaffinity and other mature cellular and enzymatic characteristics while engulfed in a fully developed and functionally active cortex [4, 5]. In contrast, extra...