This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wotus, C. Articles by Engeland, W. C. Search for Related Content PubMed PubMed Citation Articles by Wotus, C. Articles by Engeland, W. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Development of Adrenal Zonation in Fetal Rats Defined by Expression of Aldosterone Synthase and 11ß-Hydroxylase

Department of Surgery (C.W., B.K.L.-Y., L.M.R.) and of Cell Biology and Neuroanatomy (W.C.E.), University of Minnesota, Minneapolis, Minnesota 55455; Department of Medicine, Endocrine Section (C.E.G.-S.), Harry S. Truman Memorial Veterans Hospital, University of Missouri, Columbia, Missouri 65201

Address all correspondence and requests for reprints to: W. C. Engeland, Ph.D., Box 120 UMHC, 516 Delaware Street S.E., Minneapolis, Minnesota 55455.

The adult rat adrenal cortex is comprised of three concentric steroidogenic zones that are morphologically and functionally distinguishable: the zona glomerulosa, zona intermedia, and the zona fasciculata/reticularis. Expression of the zone-specific steroidogenic enzymes, cytochrome P450 aldosterone synthase (P450aldo), and P450 11ß hydroxylase (P45011ß), produced by the zona glomerulosa and zona fasciculata/reticularis, respectively, can be used to define the adrenal cortical cell phenotype of these two zones. In this study, immunohistochemistry and in situ hybridization were used to determine the ontogeny of expression of P450aldo and P45011ß to monitor the pattern of development of the rat adrenal cortex. RIA was used to measure adrenal content of aldosterone and corticosterone, the resulting products of the two enzymatic pathways. Double immunofluorescent staining for both enzymes at gestational day 16 (E16) showed P45011ß protein expressed in cells distributed throughout most of the adrenal intermixed with a separate, but smaller, population of cells expressing P450aldo protein. Whereas expression of P45011ß protein retained a similar pattern of distribution from E16 to adulthood (ignoring distribution of SA-1 positive, presumptive medullary cells), P450aldo protein changed its pattern of distribution by E19, becoming localized in a discontinuous ring of cells adjacent to the capsule. By postnatal day 1, P450aldo protein distribution was similar to that observed in adult glands; P450aldo-positive cells formed a continuous zone underlying the capsule. In situ hybridization showed that the pattern of P45011ß messenger RNA expression paralleled protein expression at all times, whereas P450aldo messenger RNA paralleled protein at E19 and after, but was undetectable before E19. However, adrenal aldosterone and corticosterone, as measured by RIA, were detected by E16, supporting the functional capacity of both phenotypes for all ages studied. These data suggest that the development of the adrenal zona glomerulosa occurs in two distinct phases; initial expression of the glomerulosa phenotype in scattered cells of the inner cortex before E17, followed by a change in distribution to the outer cortex between E17 and E19. It is hypothesized that this change in distribution occurs via cell differentiation, rather than cell migration, and that a possible regulator of these events is the fetal renin-angiotensin system.

This article has been cited by other articles:

				D. G Romero, M. Y. Zhou, L. L Yanes, M. W Plonczynski, T. R Washington, C. E Gomez-Sanchez, and E. P Gomez-Sanchez Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion J. Endocrinol., August 1, 2007; 194(2): 429 - 440. [Abstract] [Full Text] [PDF]

				I. Bogdarina, S. Welham, P. J. King, S. P. Burns, and A. J.L. Clark Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension Circ. Res., March 2, 2007; 100(4): 520 - 526. [Abstract] [Full Text] [PDF]

				W. C. Engeland, W. B. Ennen, A. Elayaperumal, D. A. Durand, and B. K. Levay-Young Zone-specific cell proliferation during compensatory adrenal growth in rats Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E298 - E306. [Abstract] [Full Text] [PDF]

				M. Venihaki, A. Carrigan, P. Dikkes, and J. A. Majzoub Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency PNAS, June 20, 2000; 97(13): 7336 - 7341. [Abstract] [Full Text] [PDF]

				H. Raff, B. M. Jankowski, E. D. Bruder, W. C. Engeland, and M. K. Oaks The Effect of Hypoxia from Birth on the Regulation of Aldosterone in the 7-Day-Old Rat: Plasma Hormones, Steroidogenesis in Vitro, and Steroidogenic Enzyme Messenger Ribonucleic Acid Endocrinology, July 1, 1999; 140(7): 3147 - 3153. [Abstract] [Full Text]