Ontogeny and sexual dimorphic expression of mouse type 2 11beta-hydroxysteroid dehydrogenase.
11beta-hydroxysteroid dehydrogenase (11beta-HSD) catalyzes the interconversion of cortisol to hormonally inactive cortisone (corticosterone (B) to 11-dehydrocorticosterone (A) in rodents), and as such is established as a pre-receptor signalling pathway for corticosteroid hormone action. To further evaluate the role of this enzyme in adult and fetal life we have characterized two isoforms of 11beta-HSD in mouse tissues. Mouse 'liver' or type 1 11beta-HSD is a bi-directional dehydrogenase/oxo-reductase (K(m) for B 1.9 microM, K(m) for A 0.73 microM). Oxo-reductase activity utilized only NADPH as a co-factor, whilst dehydrogenase activity increased with both NAD or NADP. Mouse 'kidney' or 11beta-HS3D2 activity was NAD-dependent with a K(m) for B of 0.11 microM. Dexamethasone was not a substrate. Using an in-house mouse 11beta-HSD2 cDNA and NAD-dependent activity studies, 11 beta-HSD2 was expressed in epithelial cells of colon, renal collecting ducts, ovary, and adrenal, but was absent in liver, spleen, testis and heart. With the exception of gonadal tissues, activity and mRNA levels were consistently higher in adult male versus female tissues. In fetal kidney and colon there was absent/low levels of 11beta-HSD2 expression from fetal day 15 to term (day 19/20). Placental 11beta-HSD2 mRNA and activity were highest on fetal day 13/14 and fell progressively to undetectable levels by term. Two isoforms of 11beta-HSD are present in mouse tissues in accordance with other mammalian species. The sexual-dimorphic expression 11 beta-HSD2 in kidney and colon may reflect male-female differences in sodium homeostasis, and the absent expression of 11 beta-HSD2 in late gestation may facilitate glucocorticoid-dependent maturation of mouse fetal tissues.
Condon
J
J
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, UK.
Ricketts
M L
ML
Whorwood
C B
CB
Stewart
P M
PM
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000201:enzymology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009928:Organ Specificity; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D012727:Sex Characteristics
D007527:Isoenzymes; D012333:RNA, Messenger; D009243:NAD; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases