Sex-specific response of rat costochondral cartilage growth plate chondrocytes to 17ß-estradiol involves differential regulation of plasma membrane associated estrogen receptors.
Biochim Biophys Acta
; 1833(5): 1165-72, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23305904
ABSTRACT
Both male and female rat growth plate chondrocytes express estrogen receptors (ERs); however 17ß-estradiol (E2) induces membrane responses leading to activation of phospholipase A2 (PLA2), phospholipase C (PLC), prostaglandin E2 (PGE2) production, protein kinase C (PKC), and ultimately mitogen protein kinase (MAPK) only in female cells. This study investigated if these sex-specific responses are due to differences in the actual ERs or in downstream signaling. Western blots and flow cytometry of costochondral cartilage resting zone chondrocytes (RCs) showed 2-3 times more ERα in plasma membranes (PMs) from female cells than male cells. Tunicamycin blocked E2-dependent ER-translocation to the PM, indicating palmitoylation was required. Co-immunoprecipitation showed E2 induced complex formation between ER isoforms only in female RCs. To examine if the lack of response in PKC and PGE2 in males is due to differences in signaling, we examined involvement of ERs and the role of PLC and PLA2. Selective ERα (propylpyrazole triol, PPT) and ERß (diarylproprionitrile, DPN) agonists activated PKC in female RCs only. The PLC inhibitor, U73122 blocked E2's effect on PKC and the cytosolic PLA2 inhibitor, AACOCF3 inhibited the effect on PGE2 in female RCs, confirming involvement of PLC and PLA2 in the mechanism. The PLC activator, m-3M3FßS activated PKC and PLAA peptide increased PGE2 levels in male and female RCs, showing that the signaling pathways are present. These data indicate that differences in membrane ER amount, localization, translocation and interaction are responsible for the sexual dimorphic response to E2.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cartilagem
/
Caracteres Sexuais
/
Receptor alfa de Estrogênio
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Receptor beta de Estrogênio
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Lâmina de Crescimento
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos