ACTH depletion represses vascular endothelial-cadherin transcription in mouse adrenal endothelium in vivo.
Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion protein that is localised at cell-cell contacts. This molecule is an important determinant of vascular architecture and endothelial cell survival. In the adrenal cortex, steroidogenic and endothelial cells form a complex architecture. The adrenocorticotrophin hormone (ACTH) regulates gland homeostasis whose secretion is subjected to a negative feedback by adrenocorticosteroids. The aim of the present study was to determine whether VE-cadherin expression in the adrenal gland was regulated by hormonal challenge. We demonstrated that VE-cadherin protein levels were dramatically decreased (23.5+/-3.7%) by dexamethasone injections in the mouse and were restored by ACTH within 7 days (94.9+/-18.6%). Flow cytometry analysis of adrenal cells showed that the ratios of endothelial versus total adrenal cells were identical (35%) in dexamethasone- or ACTH-treated or untreated mice, suggesting that VE-cadherin expression could be regulated by ACTH. We demonstrate the existence of a transcriptional regulation of the VE-cadherin gene using transgenic mice carrying the chloramphenicol acetyl transferase gene under the control of the VE-cadherin promoter. Indeed, the promoter activity in the adrenals, but not in the lung or liver, was decreased in response to dexamethasone treatment (40+/-1.3%) and was partially restored after gland regeneration by ACTH injection (82+/-3%). In conclusion, our results show that transcription of a specific endothelial gene is controlled by the hypothalamo-pituitary axis and the data expand the knowledge regarding the role of ACTH in the regulation of the adrenal vascular network.
Huber
Philippe
P
Laboratoire Développement et Vieillissement de l'Endothelium, INSERM EMI 02-19, DRDC/DVE, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble, Cedex 9, France.
Mallet
Christine
C
Faure
Elodie
E
Rampon
Christine
C
Prandini
Marie-Hélène
MH
Féraud
Olivier
O
Bouillot
Stéphanie
S
Vilgrain
Isabelle
I
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D004727:Endothelium / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D011401:Promoter Regions, Genetic; D000099152:Cadherin 5
D000324:Adrenocorticotropic Hormone; D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5