Patterns of long-term steroidogenesis stimulation by ACTH and phorbol ester

RESUMO

Adrenocorticotropic hormone (ACTH) triggers well-defined responses in Y-1 cells. Among them is steroidogenesis stimulation. We have previously shown that phorbol 12-myristate 13-acetate (PMA), an activator of the calcium- and phospholipid-dependent protein kinase (PKC) is able to mimic all the responses triggered by ACTH in these cells, including steroidogenesis stimulation. Short (2 h) treatment with PMA leads to only 20-30 per cent of the maximal steroidogenesis stimulation obtained with ACTH. However, the steroid secretion in the 2 h that follows the short-term (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 restricted to cells treated with PMA for up to 4 h, while treatment for longer periods of time causes a reduction of the steroid biosynthesis rate, an effect that is not observed in cells treated with ACTH or N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dcAMP). These results suggest that activation of PKC can elicit the first phase of ACTH steroidogenesis stimulation, but not the second one, which strictly depends on activation of cAMP-dependent protein kinase.