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Effect of Labor on Glucocorticoid Receptor (GRTotal, GR, and GRß) Proteins in Ovine Intrauterine Tissues

CIHR Institute of Human Development, Child and Youth Health, Departments of Physiology and Ob/Gyn, University of Toronto, Toronto, Canada; Departments of Physiology and Ob/Gyn and Program in Development and Fetal Health, Samuel Lunenfeld Institute, MSH, Toronto, Canada; Departments of Cellular and Molecular Medicine and Ob/Gyn, University of Ottawa, Ottawa, Canada; Department of Physiology, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 3344, Toronto, Ontario M5S 1A8 Canada; shalini.gupta{at}utoronto.ca

Sandor Gyomorey, MSc

Stephen J. Lye, PhD

William Gibb, PhD

John R. G. Challis, PhD

CIHR Institute of Human Development, Child and Youth Health, Departments of Physiology and Ob/Gyn, University of Toronto, Toronto, Canada; Departments of Physiology and Ob/Gyn and Program in Development and Fetal Health, Samuel Lunenfeld Institute, MSH, Toronto, Canada; Departments of Cellular and Molecular Medicine and Ob/Gyn, University of Ottawa, Ottawa, Canada

Objective: 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, GR, and GRß isoforms in ovine placenta, fetal membranes, and uterus during the onset and progression of labor.

Methods: 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, GR, and GRß by immunohistochemical and Western blot analyses.

Results: GR_Total, GR, and GRß proteins were present in trophoblast cells but not maternal tissue of the placentome. GR and ß were distinctly expressed in trophoblast nuclei and cytosol, respectively. GR_Total, GR, and GRß were also detected in amnion epithelial cells and chorionic epithelium of the fetal membranes, and the maternal endometrial epithelium. GR_Total and GR were also present in amnion mesenchymal and glandular epithelium. GR_Total and GR (95 kDa) protein levels were significantly (P < .05) higher during labor; GRß (90 kDa) levels remained unchanged.

Conclusion: 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.

Key Words: Ovine parturition • glucocorticoid receptor • GR isoform • GRß isoform

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