Increased ACTH levels do not alter renal 11beta-hydroxysteroid dehydrogenase type 2 gene expression in the sheep.
The regulation of renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene expression is poorly understood. Inhibition of expression can result in hypertension. An example of this is in ectopic adrenocorticotropin (ACTH) syndrome (EAS). Inhibition of 11betaHSD2 activity is suggested by the observed increased ratio of cortisol to cortisone in both plasma and urine. To investigate whether ACTH or ACTH-dependent steroids can modulate renal 11betaHSD2 gene expression we analysed renal 11betaHSD2 mRNA levels after treatment with ACTH of 1 H and 24 H and demonstrated no change in the levels of gene expression. We have demonstrated in this study that the expression of 11betaHSD2 in the kidney is unaltered by ACTH. The reduced inactivation of cortisol by 11betaHSD2 observed in EAS is likely to be in part due to end product inhibition or substrate overload of the enzyme by endogenous substrates (cortisol, corticosterone, etc) rather than inhibition of 11betaHSD2 at the transcriptional level by either ACTH or ACTH regulated steroids.
Albiston
A L
AL
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Matsacos
D
D
McDougall
J
J
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep
D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone