Arginine vasopressin stimulates 11beta-hydroxysteroid dehydrogenase type 2 expression in the mineralocorticosteroid target cells.
11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) deficiency causes sodium retention and severe hypertension by allowing glucocorticoids access to the non-selective mineralocorticosteroid receptor. Understanding regulation of the HSD11B2 gene is thus of fundamental importance in hypertension research. A number of studies have suggested that second messenger pathways may be important in this regard. In the present study we show that HSD11B2 expression in human renal epithelial P58 cells is regulated at the mRNA and protein level, and that protein kinases A (PKA) and C (PKC) are involved in this process. PKA stimulation resulted in almost two-fold increase while PKC activation in almost two-fold decrease in the HSD11B2 mRNA and protein level. Western blot analysis revealed a dimeric form of 11beta-HSD2 of about 80kDa. Arginine vasopressin (AVP), acting through the AVP2 receptor, as well as 11beta-HSD2 substrates, corticosterone and dexamethasone, up-regulate HSD11B2 expression, suggesting their role as possible factors affecting blood pressure. We show that the activators of the PKA pathway induce, while activators of PKC pathway repress the expression of HSD11B2 in human renal epithelial cells. AVP, acting via the PKA pathway, might be a physiological stimulator of the HSD11B2 expression. The 11beta-HSD2 substrates, both natural (corticosterone) and synthetic (dexamethasone), might protect the mineralocorticosteroid-target cells against cortisol excess.
Rubis
Blazej
B
University of Medical Sciences, Department of Biochemistry and Molecular Biology, Swiecickiego 6 Street, 60-781 Poznan, Poland.
Krozowski
Zygmunt
Z
Trzeciak
Wieslaw H
WH
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002460:Cell Line; D003345:Corticosterone / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007668:Kidney / Q000166:cytology; D008901:Mineralocorticoids / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology
D008901:Mineralocorticoids; D001127:Arginine Vasopressin; D003907:Dexamethasone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D003345:Corticosterone