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cGMP-dependent ADP depolymerization of actin mediates estrogen increase in cervical epithelial permeability.
1Departments of Reproductive Biology and Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gig@po.cwru.edu
American Journal of Physiology. Cell Physiology
|November 18, 2000
Summary
Estrogen, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) promote actin depolymerization in cervical cells. This process involves NO-induced, cGMP-dependent protein kinase enhancing actin ADP-ribosylation.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Mechanisms
Background:
- Estrogen influences cervical mucus secretion, a process linked to cytoskeletal changes.
- The precise molecular pathways of estrogen's action on the cytoskeleton remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanism by which estrogen affects the actin cytoskeleton in human cervical epithelial cells.
- To investigate the roles of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in estrogen-mediated cytoskeletal regulation.
Main Methods:
- Human cervical epithelial cells were treated with 17beta-estradiol, sodium nitroprusside (SNP), or 8-bromoguanosine 3', 5'-cyclic monophosphate (8-Br-cGMP).
- Inhibitors including tamoxifen, LY-83583 (guanylate cyclase inhibitor), and KT-5823 (cGMP-dependent protein kinase inhibitor) were used to block specific pathways.
- Changes in monomeric G-actin and polymerized F-actin were assessed, along with paracellular permeability and protein phosphorylation.
Main Results:
- 17beta-estradiol, SNP, and 8-Br-cGMP treatment led to increased G-actin and decreased F-actin, indicating actin depolymerization.
- Estrogen's effects were inhibited by tamoxifen, LY-83583, and KT-5823, suggesting involvement of NO and cGMP signaling.
- SNP and 8-Br-cGMP also induced actin depolymerization, with specific inhibitor profiles revealing distinct pathway contributions.
- These agents attenuated phosphorylation of [(32)P]adenylate NAD in vitro, with differential blockade by inhibitors.
Conclusions:
- Estrogen, NO, and cGMP collectively stimulate actin depolymerization in cervical epithelial cells.
- A proposed mechanism involves NO-mediated activation of cGMP-dependent protein kinase, which augments ADP-ribosylation of monomeric actin.
- These findings provide insight into the molecular regulation of cytoskeletal dynamics by hormones and signaling molecules.
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