Effect of labor on glucocorticoid receptor (GR(Total), GRalpha, and GRbeta) proteins in ovine intrauterine tissues.

Abstract

Activation of the fetal hypothalamic-pituitary-adrenal axis and a concurrent increase in plasma cortisol concentration plays a crucial role in parturition in sheep. The effects of cortisol on intrauterine tissues are mediated, in part, by glucocorticoid receptors (GR). In the present study, we determined the temporal and tissue-specific expression of GR(Total), GRalpha, and GRbeta isoforms in ovine placenta, fetal membranes, and uterus during the onset and progression of labor. Intrauterine tissues were collected from following three groups of pregnant ewes at term (147-149 days of gestation): animals not in labor (NIL; 140-145 days; n = 5), early labor (EL; 143-149 days; n = 6), and active labor (L; 145-149 days; n = 6). They were analyzed for GR(Total), GRalpha, and GRbeta by immunohistochemical and Western blot analyses. GR(Total), GRalpha, and GRbeta proteins were present in trophoblast cells but not maternal tissue of the placentome. GRalpha and beta were distinctly expressed in trophoblast nuclei and cytosol, respectively. GR(Total), GRalpha, and GRbeta were also detected in amnion epithelial cells and chorionic epithelium of the fetal membranes, and the maternal endometrial epithelium. GR(Total) and GRalpha were also present in amnion mesenchymal and glandular epithelium. GR(Total) and GRalpha (95 kDa) protein levels were significantly (P < .05) higher during labor; GRbeta (90 kDa) levels remained unchanged. The temporal and tissue-specific pattern of GR expression within ovine intrauterine tissues during labor implicates GR in regulating cortisol action to induce enzymatic changes controlling labor in sheep.