CGMP-dependent ADP depolymerization of actin mediates estrogen increase incervical epithelial permeability

Estrogen increases secretion of cervical mucus in women, and the effect dep ends on fragmentation of the cytoskeleton. The objective of the present stu dy was to understand the molecular mechanism of estrogen action. Treatment of human cervical epithelial cells with 17 beta -estradiol, sodium nitropru sside (SNP), or 8-bromoguanosine 3', 5'-cyclic monophosphate (8-Br-cGMP) in creased cellular monomeric G-actin and decreased polymerized F-actin. The e ffects of estradiol were blocked by tamoxifen, by the guanylate cyclase inh ibitor LY-83583, and by the cGMP-dependent protein kinase inhibitor KT-5823 . The effects of SNP were blocked by LY-83583 and KT-5823, while the effect s of 8-Br-cGMP were blocked only by KT-5823. Treatment with phalloidin decr eased paracellular permeability and G-actin. Treatment with 17 beta -estrad iol, SNP, or 8-Br-cGMP attenuated SNP-induced phosphorylation of [P-32] ade nylate NAD in vitro: tamoxifen blocked the effect of estrogen; LY-83583 blo cked the effect of SNP but not that of 8-Br-cGMP, while KT-5823 blocked eff ects of both SNP and 8-Br-cGMP. These results indicate that estrogen, nitri c oxide (NO), and cGMP stimulate actin depolymerization. A possible mechani sm is NO-induced, cGMP-dependent protein kinase augmentation of ADP-ribosyl ation of monomeric actin.