Role of Arachidonic Acid Metabolism in Acth-Stimulated Cortisol Secretion by Bovine Adrenocortical Cells

Abstract

We have studied the effects of inhibitors of arachidonic acid (AA) metabolism, nordihydroguaiaretic acid (NDGA), a lipoxygenase (LPX) inhibitor, and indomethacin (INDO), a cyclooxygenase (COX) inhibitor, on cortisol secretion and StAR protein in primary cultures of bovine adrenal zona fasciculata (ZF) cells. NDGA inhibited cortisol secretion in response to both 10⁻¹² M and 10⁻⁸ M ACTH. AA (10⁻⁴ M) partially reversed the inhibition of cortisol secretion by NDGA at 10⁻¹² M ACTH but not at 10⁻⁸ M ACTH. On the other hand, INDO potentiated the cortisol response to 10⁻¹² M ACTH. Neither NDGA nor INDO significantly affected StAR protein levels. These results suggest a StAR protein-independent role for the LPX and COX pathways in acute cortisol secretion, and support the hypothesis that LPX products of AA metabolism are key cellular signals when bovine ZF cells are acutely stimulated by physiological concentrations of ACTH (10⁻¹² M).