The phosphatidylinositide-Ca2+ hypothesis does not apply to the steroidogenic action of corticotropin.
The hypothesis that ACTH (corticotropin) stimulates steroidogenesis by a mechanism that involves breakdown of polyphosphoinositides and increase in intracellular Ca2+ (called here the 'phosphatidylinositide-Ca2+ mechanism') was tested in Y-1 adrenal-tumour cells and in bovine fasciculata cells, by using incorporation of 32P and myo-[3H]inositol to study phospholipid metabolism, and quin-2 and fura 2 to measure intracellular Ca2+. As a positive control, we repeated experiments showing that angiotensin II stimulates glomerulosa cells by way of the phosphatidylinositide-Ca2+ mechanism, by using the same methods. With Y-1 and fasciculata cells, no change was observed in the incorporation of either of the labelled precursors into any phosphatidylinositide or into any of three major phosphoinositols, i.e. inositol phosphate, bisphosphate and trisphosphate. Moreover, no change in mass of any of these compounds was seen. No change was observed in the concentration of intracellular Ca2+ in Y-1 or fasciculata cells on addition of ACTH, by using either quin-2 or fura 2. By contrast, decreased incorporation of 32P into phosphatidylinositol bisphosphate and an increase in intracellular Ca2+ were seen when glomerulosa cells were treated with angiotensin II. It is concluded that the phosphatidylinositide-Ca2+ mechanism is not used by Y-1 adrenal or bovine fasciculata cells in the steroidogenic response to ACTH unless the mechanism is radically different from that seen with all other hormones so far tested in which this mechanism occurs.
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D007424:Intracellular Fluid / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D010716:Phosphatidylinositols; D010743:Phospholipids; D000324:Adrenocorticotropic Hormone; D002118:Calcium