Prolactin blocks glucocorticoid induced cell death by inhibiting the disruption of the mitochondrial membrane

Prolactin (PRL) has been reported to inhibit dexamethasone (Dex) induced ce ll death. Nevertheless, the mechanism through which PRL exerts its protecti ve effect is still not unravelled. Here, we analyse the effect of PRL at di fferent stages of the glucocorticoid (GC) apoptotic pathway in PRL dependen t cells (Nb, cells). PRL blocks completely the GC induced loss of the mitoc hondrial transmembrane potential (Delta Psi(m))and consequently phosphatidy lserine (PS) exposure and loss of DNA content. Although PRL promotes an upr egulation of the bcl-2 expression, simultaneous addition of PRL to GC fails to maintain even the normal levels of this anti-apoptotic protein. This fi nding excludes a critical role for bcl-2 in the PRL protective effect again st GC. GC induced Delta Psi(m) disruption can be inhibited by the ICE-like inhibitor zVAD-fmk but not by ICE inhibitor tetrapeptide acetyl-Tyr-Val-Ala -Asp.chloromethylketon (YVAD-cmk) nor by caspase-3 inhibitor zDEVD. It can be speculated that PRL blocks Delta Psi(m), disruption by inhibiting an unk nown caspase activated by GC. (C) 1999 Elsevier Science Ltd. All rights res erved.