Eph receptors and zonation in the rat adrenal cortex

Abstract

Although the zonation of the adrenal cortex has a clear functional role, the mechanisms that maintain it remain largely conjectural. The concept that an outer proliferative layer gives rise to cells that migrate inwards, adopting sequentially the zona glomerulosa, fasciculata and reticularis phenotypes, has yet to be explained mechanistically. In other tissues, Eph receptor (EphR)/ephrin signalling provides a mechanism for cellular orientation and migration patterns. Real-time PCR and other methods were used to determine the possible role of Eph/ephrin systems in the rat adrenal. mRNA coding for several members of the EphR family was detected, but out of these, EphA2 provided the closest parallel to zonal organisation. In situ hybridisation showed that EphA2 mRNA and EphA protein were predominantly located in the zona glomerulosa. Its transcription closely reflected expected changes in the glomerulosa phenotype, thus it was increased after a low-sodium diet, but decreased by pretreatment with the angiotensin-converting enzyme inhibitor, captopril. It was also decreased by ACTH treatment, but unaffected by betamethasone. mRNA coding for ephrin A1, the major ligand for the EphA receptors, was also detected in the rat adrenal, though changes evoked by the various pretreatments did not clearly reflect the expected changes in zonal function. Because the maintenance of cellular zonation requires clear positional signals within the adrenal cortex, these data support a role for Eph forward and reverse signalling in the maintenance of adrenocortical zonation.

Alteration of Subcapsular Adrenocortical Zonation in Humans with Aging

“…Functional adrenal zonation has been studied extensively in rodents, with the major sites of adrenocortical proliferation described as the stem cell zone, progenitor cell zone, undifferentiated cell zone, intermediate zone, and undifferentiated zona glomerulosa (Mitani et al 1994;Mitani et al 2003;Peters et al 1998;McNeill et al 2005;Brennan et al 2008). The results of the present study in humans suggest that the zP in humans has a major role in bidirectional differentiation into either the zG or the zF according to the endocrinological environment, rather than in relation to cellular proliferative activity.…”

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

“…Among these are ephrins (EphA) and their receptors, which are mainly present in the ZG. Interestingly, the level of expression of EphA2 closely correlates with changes in the ZG phenotype, in particular it is increased in animals on a low-sodium diet (which increases ZG size), but decreased by ACTH treatment (which increases ZF size) (Brennan et al 2008). Another family of extracellular matrix proteins, thrombospondins, is expressed in bovine adrenal glands, with thrombospondin 2 (TSP2) promoting cell attachment but preventing spreading of adrenocortical cells in primary culture (Feige et al 1998).…”

Functional Zonation of the Adult Mammalian Adrenal Cortex

“…The Eph/ephrin forward-reverse signaling system provides a possible mechanism for such cellular orientation and migration within the zones, and elements of the system have been demonstrated in the rat adrenal cortex. In particular, EphA2 is strongly transcribed in the rat glomerulosa, and responds to the physiological stimuli of a low sodium diet, captopril, or betamethasone treatment in a manner that suggests association with cell phenotype (Brennan et al, 2008 ).…”