CHRONIC HYPOXEMIA SELECTIVELY DOWN-REGULATES 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2 GENE-EXPRESSION IN THE FETAL SHEEP KIDNEY

The present study was designed to examine the effects of chronic fetal placental embolization on the expression of 17 beta-hydroxysteroid de hydrogenase (11 beta-HSD) types 1 and 2, the intracellular enzymes res ponsible for the metabolism of glucocorticoids, Twelve instrumented fe tal sheep were randomly allocated on Day 110 (term = 147 days) to eith er a control (n = 6) or embolized (n = 6) group, Embolized fetuses rec eived daily injections of nonradioactive microspheres into the abdomin al aorta for 21 days to decrease arterial oxygen content by 40-50% of the pre-embolization values. At the end of the experiment, fetal liver and kidney tissues as well as placental cotyledons were collected, an d tissue levels of 11 beta-HSD mRNA and activity were determined by st andard Northern blot analysis and radiometric conversion assay, respec tively. There was a 44% reduction (p < 0.01) in the level of renal 11 beta-HSD mRNA in the embolized group as compared with the control grou p. Moreover, this reduction in mRNA was carried through to 11 beta-HSD 2. protein, since there was a corresponding decrease in the level of 1 1 beta-HSD2 activity (4.5 +/- 0.2 vs. 2.9 +/- 0.1 pmol/min per milligr am protein, p < 0.01). In contrast, levels of both 11 beta-HSD1 mRNA a nd activity in the fetal liver remained unchanged. Moreover, both 11 b eta-HSD types 1 and 2 mRNA and activity in the placenta were not alter ed by the fetal placental embolization, In conclusion, chronic hypoxem ia selectively inhibits renal 11 beta-HSD2 mRNA expression and enzyme activity in the ovine fetus, which may contribute, at least in part, t o the mechanisms leading to fetal hypertension.