Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA and glucocorticoid receptor protein during mouse embryonic development.
Accumulating evidence suggests that the actions of glucocorticoids in target tissues are critically determined by the expression of not only the glucocorticoid receptor (GR) but also the glucocorticoid-metabolizing enzymes, known as 11beta-hydroxysteroid dehydrogenase types 1 and 2 (11beta-HSD1 and 11beta-HSD2). To gain insight into the role of glucocorticoids in fetal development, the expression patterns of the two distinct 11beta-HSD isozymes and GR were studied in the mouse embryo from embryonic day 12.5 (E12.5, term = E19) to postnatal day 0.5 (P0.5) by in situ hybridization and immunohistochemistry, respectively. 11beta-HSD1 mRNA was detected in the heart as early as E12.5 and maintained thereafter. In the lung and liver, 11beta-HSD1 mRNA was first detected between E14.5 and E16.5, increased to high levels towards term and maintained after birth. Relatively low levels of 11beta-HSD1 mRNA were also detected in the kidney, adrenal glands and gastrointestinal tract at E18.5. However, the mRNA for 11beta-HSD1 was undetectable in all other embryonic tissues including the brain. In contrast, kidney was the only organ that expressed appreciable levels of 11beta-HSD2 mRNA during embryonic life. The level of 11beta-HSD2 mRNA in the kidney increased dramatically in the newborn, which coincided with expression of 11beta-HSD2 mRNA in the whisker follicle, tooth and salivary gland. Distinct from the profiles of 11beta-HSD1 and 11beta-HSD2 mRNA, GR protein was detectable in all tissues at all ages studied except for the thymus, salivary gland, and bone. Taken together, the present study demonstrates that tissue- and developmentally-stage specific expression of 11beta-HSD1 and 11beta-HSD2 as well as GR occurs in the developing mouse embryo, thus highlighting the importance of these two enzymes and GR in regulating glucocorticoid-mediated maturational events in specific tissues during murine embryonic development.
Thompson
A
A
Department of Obstetrics & Gynecologu, University of Western Ontario, London, Ont, Canada.
Han
V K M
VK
Yang
K
K
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis / Q000235:genetics*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000235:genetics; D014018:Tissue Distribution
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2