Connexins (Cx) are membrane proteins able to influence cell responses, such as proliferation, differentiation, migration, and invasiveness. Likewise, glucocorticoids (GC) are also known to modulate many factors involved in implantation, including trophoblast gap-junction intercellular communication (GJIC), although their influence on pregnancy is controversial. In order to investigate the effects of β-methasone, a synthetic glucocorticoid, on Cx and glucocorticoid receptor (GR) expression and localization, as well as on cell proliferation, the extravillous trophoblast-derived HTR-8/SVneo cell line was used as a model. Our results, confirmed by means of immunofluorescence, demonstrated that β-methasone selectively modifies GR and Cx expression, enhancing the GRα isoform without affecting GRβ, and inhibiting Cx40 expression while increasing that of Cx43 and Cx45. Furthermore, β-methasone was shown to exert an inhibitory action on cell proliferation. In our model the abortion drug RU-486 (mifepristone), reported to be a GR antagonist, did not contrast this effect of β-methasone. On the contrary, it induced responses similar to those of the hormone. Knowing that RU-486 is also a potent progesterone receptor antagonist, we then tested progesterone effect alone and in combination with the drug, on Cx expression and cell proliferation. Progesterone (P4) showed the same effect as β-methasone on Cx expression, while it did not affect proliferation. Based on our results, neither aborption effects of RU486 nor the protective action of both beta-methasone and progesterone are exerted by modulation of Cx, since at this level they induces similar changes, RU-486 did not antagonize the progesterone effect, thereby suggesting that its abortive action is not obtained through the alteration of trophoblast Cx expression.
β-methasone, progesterone and RU-486 (mifepristone) exert similar effects on connexin expression in trophoblast-derived HTR-8/SVneo cells.
CERVELLATI, Franco;PAVAN, Barbara;LUNGHI, Laura;FABBRI, Elena;BIONDI, Carla;PATELLA, Alfredo;VESCE, Fortunato
2011
Abstract
Connexins (Cx) are membrane proteins able to influence cell responses, such as proliferation, differentiation, migration, and invasiveness. Likewise, glucocorticoids (GC) are also known to modulate many factors involved in implantation, including trophoblast gap-junction intercellular communication (GJIC), although their influence on pregnancy is controversial. In order to investigate the effects of β-methasone, a synthetic glucocorticoid, on Cx and glucocorticoid receptor (GR) expression and localization, as well as on cell proliferation, the extravillous trophoblast-derived HTR-8/SVneo cell line was used as a model. Our results, confirmed by means of immunofluorescence, demonstrated that β-methasone selectively modifies GR and Cx expression, enhancing the GRα isoform without affecting GRβ, and inhibiting Cx40 expression while increasing that of Cx43 and Cx45. Furthermore, β-methasone was shown to exert an inhibitory action on cell proliferation. In our model the abortion drug RU-486 (mifepristone), reported to be a GR antagonist, did not contrast this effect of β-methasone. On the contrary, it induced responses similar to those of the hormone. Knowing that RU-486 is also a potent progesterone receptor antagonist, we then tested progesterone effect alone and in combination with the drug, on Cx expression and cell proliferation. Progesterone (P4) showed the same effect as β-methasone on Cx expression, while it did not affect proliferation. Based on our results, neither aborption effects of RU486 nor the protective action of both beta-methasone and progesterone are exerted by modulation of Cx, since at this level they induces similar changes, RU-486 did not antagonize the progesterone effect, thereby suggesting that its abortive action is not obtained through the alteration of trophoblast Cx expression.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
