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
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.