ONTOGENY AND SEXUAL DIMORPHIC EXPRESSION OF MOUSE TYPE-2 11-BETA-HYDROXYSTEROID DEHYDROGENASE

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the inter conversion of cortisol to hormonally inactive cortisone (corticosteron e (B) to 11-dehydrocorticosterone (A) in rodents), and as such is esta blished as a pre-receptor signalling pathway for corticosteroid hormon e action. To further evaluate the role of this enzyme in adult and fet al life we have characterized two isoforms of 11 beta-HSD in mouse tis sues. Mouse 'liver' or type 1 11 beta-HSD is a bi-directional dehydrog enase/oxo-reductase (K-m for B 1.9 mu M, K-m for A 0.73 mu M). Oxo-red uctase activity utilized only NADPH as a co-factor, whilst dehydrogena se activity increased with both NAD or NADP. Mouse 'kidney' or 11 beta -HS3D2 activity was NAD-dependent with a K-m for B of 0.11 mu M. Dexam ethasone was not a substrate. Using an in-house mouse 11 beta-HSD2 cDN A and NAD-dependent activity studies, 11 beta-HSD2 was expressed in ep ithelial cells of colon, renal collecting ducts, ovary, and adrenal, b ut was absent in liver, spleen, testis and heart. With the exception o f gonadal tissues, activity and mRNA levels were consistently higher i n adult male versus female tissues. In fetal kidney and colon there wa s absent/low levels of 11 beta-HSD2 expression from fetal day 15 to te rm (day 19/20). Placental 11 beta-HSD2 mRNA and activity were highest on fetal day 13/14 and fell progressively to undetectable levels by te rm. Two isoforms of 11 beta-HSD are present in mouse tissues in accord ance with other mammalian species. The sexual-dimorphic expression 11 beta-HSD2 in kidney and colon may reflect male-female differences in s odium homeostasis, and the absent expression of 11 beta-HSD2 in late g estation may facilitate glucocorticoid-dependent maturation of mouse f etal tissues. (C) 1997 Elsevier Science Ireland Ltd.