A23187 inhibits adrenal protein synthesis and the effects of adrenocorticotropin (ACTH) on steroidogenesis and phospholipid metabolism in rat adrenal cells in vitro: further evidence implicating phospholipids in the steroidogenic action of ACTH.
We examined the effects of ACTH and the Ca++ ionophore, A23187, on steroidogenesis and phospholipid metabolism during incubation of dispersed rat adrenal cells. Increasing doses of ACTH elicited nearly parallel increases in corticosterone production and adrenal inositide (mono- and di-) concentrations. As reported previously by other investigators in Y1 cells, A23187 inhibited ACTH- and cAMP-stimulated, but not basal or pregnenolone-stimulated, corticosterone production. A23187 also inhibited ACTH-induced increases in phosphatidic acid, phosphatidylinositol, and diphosphoinositide, and this was attended by inhibition of [3H]leucine incorporation into protein. These findings support our previous contentions that: 1) a labile protein is required for ACTH-induced increases in adrenal phospholipids in the phosphatidate-polyphosphoinositide-polyglycerophospholipid pathway; and 2) these phospholipids are involved in the steroidogenic action of ACTH.
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D011284:Pregnenolone / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D010743:Phospholipids; D000001:Calcimycin; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone