PMID- 12642869
OWN - NLM
STAT- MEDLINE
DCOM- 20030422
LR  - 20061115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 11
DP  - 2003 Mar 20
TI  - Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human 
      pituitary adenomas: a prereceptor determinant of pituitary cell proliferation.
PG  - 1663-7
AB  - The physiological effects of glucocorticoids (GCs) are, at least in part, 
      mediated by inhibition of cell proliferation. Two isozymes of 11 
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) interconvert cortisol (F) and 
      inactive cortisone (E), and are thus able to modulate GC action at an autocrine 
      level. Previously, we have demonstrated absent expression of 11 beta-HSD2 in 
      normal pituitaries; however, in a small number of pituitary tumors analysed, 11 
      beta-HSD2 was readily demonstrable. Here we have used real-time RT-PCR to 
      quantify expression of mRNA for 11 beta-HSD1 and 2 in 105 human pituitary tumors 
      and have performed enzyme expression and activity studies in primary pituitary 
      cultures. Overall, pituitary tumors expressed lower levels of 11 beta-HSDl mRNA 
      compared with normals (0.2-fold, P<0.05). In contrast, expression of 11 beta-HSD2 
      mRNA was 9.8-fold greater in tumors than in normals (P<0.001). Enzyme assays 
      showed significant 11 beta-HSD2 activity (71.9+/-22.3 pmol/h/mg protein 
      (mean+/-s.d.)) but no detectable 11 beta-HSDl activity. Proliferation assays 
      showed that addition of glycyrrhetinic acid (an 11 beta-HSD2 inhibitor) resulted 
      in a 30.3+/-7.7% inhibition of cell proliferation. In summary, we describe a 
      switch in expression from 11 beta-HSDl to 11 beta-HSD2 in neoplastic pituitary 
      tissue. We propose that abnormal expression of 11 beta-HSD2 acts as a 
      proproliferative prereceptor determinant of pituitary cell growth, and may 
      provide a novel target for future tumor therapy.
FAU - Rabbitt, E H
AU  - Rabbitt EH
AD  - Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, 
      Birmingham, UK.
FAU - Ayuk, J
AU  - Ayuk J
FAU - Boelaert, K
AU  - Boelaert K
FAU - Sheppard, M C
AU  - Sheppard MC
FAU - Hewison, M
AU  - Hewison M
FAU - Stewart, P M
AU  - Stewart PM
FAU - Gittoes, N J L
AU  - Gittoes NJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA Primers)
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  - Adenoma/*enzymology/pathology
MH  - Base Sequence
MH  - *Cell Division
MH  - DNA Primers
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/*genetics
MH  - Pituitary Neoplasms/*enzymology/pathology
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/03/19 04:00
MHDA- 2003/04/23 05:00
CRDT- 2003/03/19 04:00
PHST- 2003/03/19 04:00 [pubmed]
PHST- 2003/04/23 05:00 [medline]
PHST- 2003/03/19 04:00 [entrez]
AID - 1206293 [pii]
AID - 10.1038/sj.onc.1206293 [doi]
PST - ppublish
SO  - Oncogene. 2003 Mar 20;22(11):1663-7. doi: 10.1038/sj.onc.1206293.