MUTATIONS IN THE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-II ENZYME ASSOCIATED WITH HYPERTENSION AND POSSIBLY STILLBIRTH

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol into cortisone, thus preventing occupation of the n on-selective mineralocorticoid receptor by glucocorticoids in the kidn ey. Placental 11 beta HSD2 is also thought to protect the fetus from t he high maternal circulating levels of glucocorticoids. Mutations gene rating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME) - a lo w renin form of hypertension. Recently, a mutation has been identified in a family with AME and in which there is a high incidence of stillb irths. In this study we have expressed the R374X mutation and show tha t the mutant is devoid of enzyme activity in intact mammalian cells ex pressing a significant level of the truncated protein. While this obse rvation elucidates the cause of AME in this family the degree to which R374X also contributes to the higher incidence of failed pregnancies remains to be determined.