PMID- 8547169
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  - Placental 11 beta-hydroxysteroid dehydrogenase and the programming of 
      hypertension.
PG  - 447-55
AB  - Excessive foetal exposure to glucocorticoids retards growth and "programmes" 
      adult hypertension in rats. Placental 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD), which catalyses the conversion of corticosterone and cortisol to inert 
      11 keto-products, normally protects the foetus from excess maternal 
      glucocorticoids. In both rats and humans there is considerable natural variation 
      in placental 11 beta-HSD, and enzyme activity correlates with birth weight. 
      Moreover, inhibition of placental 11 beta-HSD in the rat reduces birth weight and 
      produces hypertensive adult offspring, many months after prenatal treatment with 
      enzyme inhibitors; these effects are dependent upon maternal adrenal products. 
      These data suggest that placental 11 beta-HSD, by regulating foetal exposure to 
      maternal glucocorticoids, crucially determines foeto-placental growth and the 
      programming of hypertension. Maternal protein restriction during pregnancy also 
      produces hypertensive offspring and selectively attenuates placental 11 beta-HSD 
      activity. Thus, deficiency of the placental barrier to maternal glucocorticoids 
      may represent a common pathway between the maternal environment and 
      foeto-placental programming of later disease. These data may, at least in part, 
      explain the human epidemiological observations linking early life events to the 
      risk of subsequent hypertension. The recent characterization, purification and 
      cDNA cloning of a distinct human placental 11 beta-HSD (type 2) will aid the 
      further study of these intriguing findings.
FAU - Seckl, J R
AU  - Seckl JR
AD  - University of Edinburgh, Department of Medicine, Western General Hospital, 
      Edinburgh, U.K.
FAU - Benediktsson, R
AU  - Benediktsson R
FAU - Lindsay, R S
AU  - Lindsay RS
FAU - Brown, R W
AU  - Brown RW
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Glucocorticoids)
RN  - 0 (Growth Substances)
RN  - 0 (Insulin)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Female
MH  - Gene Expression Regulation
MH  - Glucocorticoids/physiology
MH  - Growth Substances/physiology
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Hypertension/embryology/enzymology/*etiology
MH  - Infant, Low Birth Weight
MH  - Infant, Newborn
MH  - Insulin/physiology
MH  - Maternal-Fetal Exchange
MH  - Placenta/*enzymology
MH  - Pregnancy
RF  - 104
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)00193-x [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1995 Dec;55(5-6):447-55. doi: 
      10.1016/0960-0760(95)00193-x.