PMID- 8547171
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  - Type 2 11 beta-hydroxysteroid dehydrogenase in foetal and adult life.
PG  - 465-71
AB  - Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyse the 
      interconversion of active cortisol to inactive cortisone; 11 beta-HSD1 is a low 
      affinity, NADP(H)-dependent dehydrogenase/oxo-reductase, and 11 beta-HSD2 a high 
      affinity, NAD-dependent dehydrogenase. Because of the importance of 11 beta-HSD 
      in regulating corticosteroid hormone action, we have analysed the distribution of 
      the 11 beta-HSD isoforms in human adult and foetal tissues (including placenta), 
      and, in addition have performed a series of substrate specificity studies on the 
      novel, kidney 11 beta-HSD2 isoform. Using an RT-PCR approach, we failed to detect 
      11 beta-HSD1 mRNA in any human mid-gestational foetal tissues. In contrast 11 
      beta-HSD2 mRNA was present in foetal lung, adrenal, colon and kidney. In adult 
      tissues 11 beta-HSD2 gene expression was confined to the mineralocorticoid target 
      tissues, kidney and colon, whilst 11 beta-HSD1 was expressed predominantly in 
      glucocorticoid target tissues, liver, lung, pituitary and cerebellum. In human 
      kidney homogenates, 11-hydroxylated progesterone derivatives, glycyrrhetinic 
      acid, corticosterone and the "end products" cortisone and 
      11-dehydrocorticosterone were potent inhibitors of the NAD-dependent conversion 
      of cortisol to cortisone. Finally high levels of 11 beta-HSD2 mRNA and activity 
      were observed in term placentae, which correlated positively with foetal weight. 
      The tissue-specific distribution of the 11 beta-HSD isoforms is in keeping with 
      their differential roles, 11 beta-HSD1 regulating glucocorticoid hormone action 
      and 11 beta-HSD2 mineralocorticoid hormone action. The correlation of 11 
      beta-HSD2 activity in the placenta with foetal weight suggests, in addition, a 
      crucial role for this enzyme in foetal development, possibly in mediating 
      ontogeny of the foetal hypothalamo-pituitary-adrenal axis.
FAU - Stewart, P M
AU  - Stewart PM
AD  - Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
FAU - Whorwood, C B
AU  - Whorwood CB
FAU - Mason, J I
AU  - Mason JI
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (DNA Primers)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Steroids)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adrenal Glands/*embryology
MH  - Adult
MH  - Base Sequence
MH  - Birth Weight
MH  - DNA Primers/chemistry
MH  - Fetus/*enzymology
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Molecular Sequence Data
MH  - Placenta/anatomy & histology/*enzymology
MH  - RNA, Messenger/genetics
MH  - Steroids/*biosynthesis
MH  - Substrate Specificity
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)00195-6 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1995 Dec;55(5-6):465-71. doi: 
      10.1016/0960-0760(95)00195-6.