PMID- 8547170
OWN - NLM
STAT- MEDLINE
DCOM- 19960220
LR  - 20190830
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 55
IP  - 5-6
DP  - 1995 Dec
TI  - The human 11 beta-hydroxysteroid dehydrogenase type II enzyme: comparisons with 
      other species and localization to the distal nephron.
PG  - 457-64
AB  - Effective glucocorticoid inactivation is currently thought to be an indispensable 
      feature of mineralocorticoid target cells. The enzyme 11 beta-hydroxysteroid 
      dehydrogenase (11 beta-HSD) inactivates glucocorticoids and prevents them from 
      binding to the non-selective mineralocorticoid receptor. In the kidney it is the 
      NAD dependent high affinity isoform (11 beta-HSD2) which is thought to endow 
      specificity on the receptor. The recent cloning of the human, sheep and rabbit 11 
      beta-HSD2 enzymes permits a comparison of the enzyme from the three species. 
      Human and rabbit enzymes are 87% identical and of similar length, while the human 
      and sheep enzymes have only 75% identity. The last 12 residues in all three 
      species were found to be highly divergent, but most of the ovine dishomology can 
      be accounted for by the deletion of a single nucleotide toward the C-terminus of 
      the protein resulting in a shift in reading frame generating a protein 27 
      residues longer than the human isoform. Numerous other deletions were also 
      observed in this region of the sheep cDNA sequence. Furthermore, the rabbit cDNA 
      also displayed a large degree of dishomology with the human sequence a short 
      distance downstream from the termination codon. Conserved overlapping cytoplasmic 
      translocation signals were observed in all three species, suggesting a topology 
      whereby the enzyme is anchored into the endoplasmic reticulum by multiple 
      hydrophobic regions in the N-terminus and the bulk of the 11 beta-HSD2 peptide is 
      sited in the cytoplasm. A polyclonal antibody generated against the C-terminus of 
      human 11 beta-HSD2 was used to localize the enzyme within the kidney. A high 
      level of immunoreactive was observed in distal tubules and collecting ducts, 
      localizing the enzyme to the same part of the nephron as the mineralocorticoid 
      receptor. Moderate levels of staining were also seen in vascular smooth muscle 
      cells. These results support the notion that 11 beta-HSD2 is an autocrine 
      protector of the mineralocorticoid receptor and that it plays an important role 
      in cardiovascular homeostatic mechanisms.
FAU - Krozowski, Z
AU  - Krozowski Z
AD  - Laboratory of Molecular Hypertension, Baker Institute of Medical Research, 
      Prahran, Australia.
FAU - Albiston, A L
AU  - Albiston AL
FAU - Obeyesekere, V R
AU  - Obeyesekere VR
FAU - Andrews, R K
AU  - Andrews RK
FAU - Smith, R E
AU  - Smith RE
LA  - eng
SI  - GENBANK/U14631
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - Genes
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - Immunoenzyme Techniques
MH  - Isoenzymes/metabolism
MH  - Kidney/*enzymology
MH  - Kidney Tubules, Distal/enzymology
MH  - Microsomes/enzymology
MH  - Molecular Sequence Data
MH  - RNA, Messenger/genetics
MH  - Rabbits
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Sheep
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - 10.1016/0960-0760(95)00194-8 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1995 Dec;55(5-6):457-64. doi: 
      10.1016/0960-0760(95)00194-8.