PROTEIN SERINE/THREONINE PHOSPHATASE 2A ACTIVITY IS INHIBITED BY cAMP IN MA-10 CELLS

CECILIA PODEROSO, CRISTINA PAZ, ALEJANDRA GOROSTIZAGA, FABIANA CORNEJO MACIEL, CARLOS F. MENDEZ, AND

San Francisco, USA

Congreso; X Adrenal Cortex Conference; 2002

PP1 and PP2A are members of the protein serine/threonine phosphatases (PPs) family and their activities have been proposed as a requirement for hormone- and cAMP-regulated steroid synthesis. These findings raise the question whether the PPs activity is increased by hormonal action in steroidogenic systems. Thus, the aim of the study was to evaluate the action of cAMP on the activity of PP1 and PP2A in MA-10 Leydig cells. Our results demonstrate that 8Br-cAMP stimulation produces a transient inhibition of PP2A activity. In contrast, PP1 activity remains unchangeable. As reported in other steroidogenic cells, cAMP-induced steroidogenesis in MA-10 cells is reduced by Cantharidin (Can) and also by Calyculin A (CA), two chemically unrelated PP1/PP2A inhibitors (data not shown). Taking into account the inhibitory effect of cAMP treatment on PP2A activity, the latest findings result paradoxical. Therefore, we next evaluated the action of these compounds on total protein synthesis. Can 10-5-5M and CA 10-7M markedly reduced total protein synthesis (35 and 50% respectively) in MA-10 cells, measured by 35S-methonine incorporation. These results suggest that hormone-dependent steroidogenesis is working through inhibition of PP2A-dependent dephosphorylation and the effect of PP1/PP2A inhibitors on steroidogenesis may be due to a general inhibition of protein synthesis rather than to a specific action on StAR protein induction.