EFFECT OF TWO PROSTAGLANDIN SYNTHESIS INHIBITORS, INDOMETHACIN AND ACETYLSALICYLIC ACID, ON PLASMA ACTH AND CORTISOL LEVELS IN MAN

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Abstract
The possible role of prostaglandins (PG) in the control of the hypothalamic-pituitary-adrenocortical axis in normal volunteers was investigated. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical production. PG apparently enhances hypothalamic CRF [corticotropin releasing factor] release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.