Indomethacin blocks gonadotropin stimulation of ovarian ornithine decarboxylase activity by inhibiting protein synthesis

Both gonadotropins and prostaglandins stimulate the ornithine decarboxylase (ODC) activity of porcine granulosa cells in vitro (1,2). To investigate a possible intermediary role of prostaglandins in this gonadotropin action, the effects of indomethacin on gonadotropin-induced ODC activity were studied. Indomethacin had no effect at concentrations lower than 10^-5 M; at higher concentrations indomethacin exerted a dose-dependent suppression of LH-stimulated ODC activity which was essentially complete at 5 × 10^-4 M. The effects of PGE₂ and 8-Bromo-cAMP, potent stimulators of ODC, were also blocked by indomethacin (5 × 10^-4 M). This effect did not represent direct inhibition of enzyme activity, but appeared to be due to inhibition of protein synthesis by the drug. Thus, incorporation of ¹⁴C-leucine into proteins by these cells was blocked by indomethacin with a dose-response curve similar to that for ODC suppression. This distal effect of indomethacin may complicate the interpretation of some experiments if the inhibitor is assumed to act only at the prostaglandin synthetase step.