Functional cross-talk between the glucocorticoid and the progestin receptors.

MARINI, M; OGARA M.F; STORTZ MD,; LEVI, V; PECCI A .

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

SAIB

The glucocorticoid and progestin receptors (GR and PR, respectively) share many similar structural and functional characteristics however the cognate hormones display distinct physiological responses. In the mammary gland, the activation of PR is associated with cell proliferation and tumor progression while activated GR is known to favor cell differentiation. The objective of this work was to evaluate whether the activated GR affects the progestin-dependent proliferation of tumoral mammary epithelial cells expressing both receptors. To assess if PR and GR have the potential to form complexes in vivo, T47D cells were transfected with expression vectors encoding for both receptors fused to fluorescent proteins (eGFPPR and mCherryGR) and incubated with Dex and/or R5020. Then, a cross-correlation analysis of the intensity fluctuations was performed in living cells by confocal microscopy. In the absence of hormone, a brightness cross-correlation (Bcc) distribution centered on zero between eGFPPR and mCherryGR particles was observed, indicating an absence of interaction. However, in the presence of R5020 or Dex mCherryGR and eGFPPR showed a positive Bcc value, suggesting that hormonal treatment induces PR/GR complex formation. Moreover, fluorescence correlation spectroscopy (FCS) studies revealed that not only GR activation but also its overexpression decrease the population and the residence time of PR binding to nuclear fixed sites, suggesting that GR would impair PR interactions with its targets. These results correlate with interference of GR on the PR-dependent expression of certain genes involved in cell proliferation