Inhibition of corticotropin secretion by hypothalamic administration of indomethacin.

The importance of endogenous prostaglandins (PGs) in regulating CRF release was investigated by administering the PG synthesis inhibitor, indomethacin (Ind), in specific hypothalamic regions to adult female rats. Solid Ind pellets placed in the anterior hypothalamic area (AHA) significantly reduced the elevated levels of plasma corticosterone normally observed after the surgical stress of the stereotaxic procedure. Similar pellets placed in the hypothalamic median eminence region (ME) completely blocked the normal compensatory hypertrophy observed 48 h after unilateral adrenalectomy. Plasma corticosterone secretion in response to hemorrhage (1% b.w.) or laparotomy with intestinal manipulation (LAP) in dexamethasone pretreated rats was reduced by Ind pellets, or Ind in phosphate buffer (BUF), respectively, implanted 2 h prior to the stress. These data suggest that the PGs may be important in mediating CRF release in response to a variety of stimuli.