Ž . Comparative Biochemistry and Physiology Part C 131 2002 3950 Absence of type 1 11-hydroxysteroid dehydrogenase enzyme in koala liver Sandra Kong, Ross A. McKinnon, Behnaz Mojarrabi, Ieva Stupans  Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences, Uni  ersity of South Australia, North Terrace, Adelaide, SA 5000, Australia Received 9 April 2001; received in revised form 26 September 2001; accepted 8 October 2001 Abstract Ž . The 11-hydroxysteroid dehydrogenases 11-HSDs interconvert 11-hydroxysteroids such as cortisol into 11-oxo- steroids such as cortisone. In most mammals, 11-HSD 1 is expressed predominantly in the liver and is active in both Ž . Ž . the oxidative cortisol to cortisone and dehydrogenase cortisone to cortisol directions, whilst 11-HSD 2 is expressed predominantly in the kidney and functions as a pure oxidative enzyme. We have investigated 11-HSD 1 activity in the Ž . Ž . Australian koala Phascolarctos cinereus and have found no activity either reductive or oxidative in hepatic microsomes. Immunoblot analysis of koala hepatic microsomes, using an 11-HSD 1 antibody raised against the mouse Ž . enzyme, failed to identify immunoreactive protein. Reverse transcriptase  polymerase chain reaction RT-PCR of koala liver mRNA and genomic PCR using primers designed against highly conserved regions of 11-HSD 1 nucleotide sequences were also negative. Furthermore, Southern and Northern blot analysis of koala genomic DNA and mRNA, respectively, confirmed that the koala lacks the 11-HSD 1 gene and gene transcript. These results support the fact that the lack of hepatic 11-HSD 1 activity in the koala is due to the absence of the 11-HSD 1 gene, and this absence is novel among mammalian species studied to date.  2002 Elsevier Science Inc. All rights reserved. Keywords: 11-Hydroxysteroid dehydrogenase; Hydroxysteroid oxidoreductase; Cortisone; Cortisol; Deficiency; Koala; Marsupial; Microsomal; Liver; Enzyme 1. Introduction Glucocorticoids play a fundamental role in the differentiation and growth of animal tissues by modulating gene expression. The enzymes re- sponsible for the interconversion of active 11-  Corresponding author. Tel.: 61-8-8302-2380; fax: 61- 8-8302-2389. Ž . E-mail address: ieva.stupans@unisa.edu.au I. Stupans . Ž hydroxysteroids such as cortisol in human 11-de- . hydroxycorticosterone in rats and 11-oxosteroids Ž . such as cortisone or corticosterone are the 11- Ž . hydroxysteroid dehydrogenases 11-HSDs . Two isoforms, type 1 and type 2, have been cloned Ž . reviewed in Krozowski et al., 1999 . These two isoforms act in an antagonistic manner with re- gards to endogenous substrates, the type 1 en- zyme acts mainly as a reductase, producing active hormones while the type 2 enzyme works in the opposite direction, converting active hormones 1532-045602$ - see front matter  2002 Elsevier Science Inc. All rights reserved. Ž . PII: S 1 5 3 2 - 0 4 5 6 01 00278-2