Acute hypoxia increases ornithine decarboxylase activity and polyamine concentrations in fetal rat brain.

Abstract

The cellular responses to hypoxia are poorly understood. To test the hypothesis that ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) activity and polyamine concentrations change in response to acute hypoxia, we performed the following studies. Pregnant Sprague-Dawley rats inspired various O2 concentrations (9-21%) for various time periods (0.5-48 h) from days 15 to 21 of gestation. In fetal brains we measured the activity of ODC, ODC mRNA, and polyamines. In response to 4-h acute mild hypoxia, ODC activity in fetal rat brain (cerebrum, cerebellum, and hippocampus) increased to 330-450% from control values (P < 0.001), after which it declined to control levels in 6-8 h. The 4-h ODC response varied inversely with inspired O2 concentration and was not mimicked by beta 2 agonist or blocked by beta 2-antagonist administration. The ODC response was associated with an increase in fetal brain putrescine concentration to 190% above control at 4-6 h (P < 0.01) and an increase in the polyamines spermidine and spermine to about 115% above control at 6-8 h. We also observed that ODC mRNA increased significantly after 2-4 h of hypoxia. ODC activity and polyamine concentrations appear to be useful enzymatic markers for fetal brain hypoxia. The magnitude and time course of the acute hypoxic ODC increase were similar to responses to extracellular signals that result in differentiation or cell growth. Thus, the well-defined and regulated ODC activity response may represent a protective mechanism in brain to hypoxia.