The adrenal gland is composed of the medulla (neurodermal origin) and the cortex (mesodermal origin). The cortex is further subdivided into three zones: zona glomerulosa (zG), zona fasciculata (zF) and zona reticularis (zR). The zones of the cortex are functionally characterised by their ability to synthesise different steroids and consequently they express different steroidogenic enzymes. These and other markers of the zones have been described but so far no good candidate for a determining factor of zonal establishment has been discovered. Bone morphogenetic proteins (BMPs) are multifunctional cytokines belonging to the transforming growth factor-β (TGF-β) superfamily. In a microarray analysis of transcripts from the zG and zF, we have discovered that some BMPs are potentially ZG specific. Various members of the BMP family and their receptors were further analysed by Real-Time PCR, using rat adrenal zG and zF tissues, and some showed preferential or exclusive expression in zG. These results were also seen in H295R cells (human adrenocorticocarcinoma cell line) after the cells had been differentiated into a zG (by Angiotensin II) and zF (by Forskolin) phenotype. These observations suggest a possible involvement of BMP signalling in the establishment of the adrenal zG. In order to investigate this further, we have influenced H295R differentiation by the addition of exogenous BMPs and blocked endogenous BMPs by siRNA. We have also confirmed the Real-Time PCR results by immunohistochemistry and Western blotting.
01 - 05 Apr 2006
European Society of Endocrinology