title: Rapid estrogen signalling in mouse primordial germ cells.
abstract: We report here that in the mouse embryonic gonads in addition to gonadal somatic cells, primordial germ cells (PGCs) the precursors of adult gametes, express estrogen receptor alpha (ERalpha) and that through this receptor, 17-beta-estradiol (E2) is able to modulate in such cells molecular signalling known to be crucial for their development. We demonstrated that PGCs from 11.5 to 12.5 days post coitum (dpc) mouse embryos express ERalpha transcripts and protein and that at concentrations of 10(-8)M E2 stimulates rapid (within 20 min) about 4-fold AKT (Ser473) and 3-fold ERK2 (Thr202/Tyr204) and SRC (Tyr418) phosphorylation. In addition, the E2 stimulatory effects were associated with increased phosphorylation of the KIT receptor (Tyr568/570). While the ER antagonist ICI182780 was able to abolish these effects, AKT phosphorylation induced by E2 was also inhibited by the PI3K inhibitor LY294002 and the SRC family inhibitor PP2. This latter was also able to abolish the increased phosphorylation of KIT and ERKs caused by E2. Taken together these results suggest that E2 may modulate via ERalpha non-genomic signalling/phosphorylation cascade in mouse PGCs. This was also supported by the finding that PGCs express MNAR, a scaffold protein that regulate ER activation in other cell types. Finally, we found that when PGCs were cultured in the presence of 10(-8)M E2 a significant ICI inhibitable increase of their number occurred. The present study provides evidence for novel direct non-genomic actions of estrogens on PGCs and suggests that these cells can represent a potential target for estrogens and estrogenic compounds during the early stages of embryo development in mammals.
authors.affiliation: Department of Public Health and Cell Biology, Section of Histology and Embryology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: La Sala
authors.forename: Donatella
authors.initials: D
authors.lastname: Farini
authors.forename: Massimo
authors.initials: M
authors.lastname: De Felici
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism*; D005865:Gestational Age; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger; D004958:Estradiol; D019009:Proto-Oncogene Proteins c-kit; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases