@entity701 to XXXX : glucocorticoid to mineralocorticoid.

@entity1 @entity2125 @entity821 @entity1369 @entity95 @entity1110 @entity2819 @entity701 @entity19672 @entity11331
@entity11331 dehydrogenase (11 beta-HSD), by converting @entity701 and @entity2819 to hormonally inactive @entity821 and @entity19672 , respectively, is an important pre-receptor signaling pathway for the renal mineralocorticoid receptor (MR). This receptor has an equal affinity for the glucocorticoids, @entity701 and @entity2819 , and for the mineralocorticoid, @entity1369 . In states of 11 beta-HSD deficiency such as the syndrome of apparent mineralocorticoid excess (AME) and licorice ingestion, @entity701 acts as a potent mineralocorticoid. In addition to the established and cloned type I 11 beta-HSD, a second 11 beta-HSD isoform has been reported in @entity95 kidney and @entity1 placenta. We have analyzed the kinetics of 11 beta-HSD activity in @entity1 kidney and compared it with the expressed @entity1 type I 11 beta-HSD cDNA. Microsomes were prepared from mid-gestational @entity1 fetal kidneys and incubated with various concentrations of @entity701 (0.0125-10 microM) and @entity2125 or @entity1110 . Kinetic analysis revealed a high affinity (apparent Km 60 nM) isoform, the activity of which was exclusively NAD-dependent. No convincing @entity1110 -dependent activity was seen. Similarly with @entity821 as a substrate no 11-oxoreductase activity was evident. In contrast, when type I @entity1 11 beta-HSD was ligated into the expression vector pcDNAI and transiently transfected into COS-I cells, low affinity (apparent Km 2.1 microM) @entity1110 -dependent activity was seen. 11-Oxoreductase activity was also observed. The cloned type I @entity1 11 beta-HSD encodes an enzyme with both low-affinity, @entity1110 -dependent, dehydrogenase and 11-oxoreductase activities, but this activity is absent in @entity1 fetal kidney (and probably adult kidney).(ABSTRACT TRUNCATED AT 250 WORDS)
