Rat 11 beta-hydroxysteroid dehydrogenase type 2 enzyme is expressed at low levels in the placenta and is modulated by adrenal steroids in the kidney.
The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) protects the non-discriminating mineralocorticoid receptor from occupation by glucocorticoids. In man the enzyme is also highly expressed in the placenta where it is thought to also protect the fetus from the high circulating levels of maternal glucocorticoids. Mutations in the HSD11B2 gene have recently been shown to account for the syndrome of apparent mineralocorticoid excess. In the present study we have used a rat 11 beta HSD2 cDNA to study the distribution and regulation of this enzyme. The rat protein is highly homologous to the mouse, rabbit and human enzymes, except for the carboxy-terminal region which displays extensive divergence between species beyond residue 382. Northern blot analysis of rat total RNA showed that the single copy gene is highly expressed in kidney and adrenal with lower levels in the colon; surprisingly, there was no detectable signal in the placenta. There was also no detectable mRNA in the liver, heart, hippocampus, testis, thymus and pancreas. Nuclease protection analysis revealed the presence of moderate 11 beta HSD2 message levels in the parotid and exceedingly low levels in the placenta. Regulation studies showed that administration of dexamethasone, deoxycorticosterone and 9 alpha-fluorocortisol to adrenalectomized rats for 7 days increased renal enzyme activity 33%-50%, while message levels decreased 35%-70%, suggesting that the increased enzyme activity may represent activation of latent enzyme.
Li
K X
KX
Laboratory of Molecular Hypertension, Baker Institute of Medical Research, Prahran, Vic., Australia.
Smith
R E
RE
Ferrari
P
P
Funder
J W
JW
Krozowski
Z S
ZS
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005438:Fludrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010920:Placenta / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D003900:Desoxycorticosterone; C021057:2 alpha-methyl-9 alpha-fluorocortisol; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D005438:Fludrocortisone