PATTERNS OF LONG-TERM STEROIDOGENESIS STIMULATION BY ACTH AND PHORBOLESTER

Adrenocorticotropic hormone (ACTH) triggers well-defined responses in Y-1 cells. Among them is steroidogenesis stimulation. We have previous ly shown that phorbol 12-myristate 13-acetate (PMA), an activator of t he calcium- and phospholipid-dependent protein kinase (PKC) is able to mimic all the responses triggered by ACTH in these cells, including s teroidogenesis stimulation. Short (2 h) treatment with PMA leads to on ly 20-30% of the maximal steroidogenesis stimulation obtained with ACT H. However, the steroid secretion in the 2 h that follows the short-te rm (2 h) PMA treatment reaches the same levels as observed with ACTH, i.e., a 12- to 15-fold increase. We also show that this effect is rest ricted to cells treated with PMA for up to 4 h, while treatment for lo nger periods of time causes a reduction of the steroid biosynthesis ra te, an effect that is not observed in cells treated with ACTH or N-6,2 '-O-dibutyryladenosine 3',5'-cyclic monophosphate (dcAMP). These resul ts suggest that: activation of PKC can elicit the first phase of ACTH steroidogenesis stimulation, but not the second one, which strictly de pends on activation of cAMP-dependent protein kinase.