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

Citation
Kxz. Li et al., 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, Molecular and cellular endocrinology, 120(1), 1996, pp. 67-75
Citations number
46
Categorie Soggetti
Endocrynology & Metabolism","Cell Biology
ISSN journal
03037207
Volume
120
Issue
1
Year of publication
1996
Pages
67 - 75
Database
ISI
SICI code
0303-7207(1996)120:1<67:R1DTEI>2.0.ZU;2-N
Abstract
The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) protects the non-discriminating mineralocorticoid receptor from occup ation by glucocorticoids. In man the enzyme is also highly expressed i n 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 a pparent 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; surpri singly, there was no detectable signal in the placenta. There was also no delectable mRNA in the liver, heart, hippocampus, testis, thymus a nd pancreas. Nuclease protection analysis revealed the presence of mod erate 11 beta HSD2 message levels in the parotid and exceedingly low l evels in the placenta. Regulation studies showed that administration o f dexamethasone, deoxycorticosterone and 9 alpha-fluorocortisol to adr enalectomized 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.