The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development.
Glucocorticoids play important roles in development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed category of 11 beta-hydroxysteroid dehydrogenase type2 (11 beta-HSD2, which potently inactivates glucocorticoids) and the mineralocorticoid receptor (MR) by in situ hybridisation from embryonic day 9.5 (E9.5, term = E19) until after birth in the mouse. Widespread abundant 11 beta-HSD2 mRNA expression from E9.5-E12.5 changes dramatically at approximately E13 to a limited tissue-specific pattern (kidney, hindgut, testis/bile ducts, lung and a few brain regions (later seen in cerebellum, thalamus, roof of midbrain, neuroepithelial regions in pons and near the subicular hippocampus)). Placenta (labyrinthine zone) and extra-embryonic membranes express abundant 11 beta-HSD2 mRNA until E15.5 but this ceases = E16.5. It is unclear to what extent rodent term placental 11 beta-HSD activity is due to persisting 11 beta-HSD2 protein. Convincing MR mRNA expression is seen from E13.5 and includes pituitary, heart, muscle and meninges with expression later in gut, kidney, thymus, discrete areas of lung and several brain regions (including hippocampus, rhinencephalon and hypothalamus). 11 beta-HSD2 and MR clearly co-localise = E18.5 in kidney and colon and might do so in discrete areas of lung (E14-15) and neuroepithelia near the subicular hippocampus. Probably elsewhere MR are non-selective and 11 beta-HSD2 is involved in protecting glucocorticoid receptors in fetal fetal tissues. Comparison with previous enzymology studies suggest the changing pattern of 11 beta-HSD2 mRNA is likely to be translated into enzyme activity and have significant parallels in human development.
Brown
R W
RW
University Department of Medicine, Centre for Genome Research, Edinburgh.
Diaz
R
R
Robson
A C
AC
Kotelevtsev
Y V
YV
Mullins
J J
JJ
Kaufman
M H
MH
Seckl
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000502:physiology*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000196:embryology / Q000235:genetics; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D005938:Glucocorticoids; D018161:Receptors, Mineralocorticoid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases