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

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Abstract

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 GRTotal, GRα, and GRβ 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 GRTotal, GRα, and GRβ by immunohistochemical and Western blot analyses.

Results

GRTotal, GRα, and GRβ proteins were present in trophoblast cells but not maternal tissue of the placentome. GRα and β were distinctly expressed in trophoblast nuclei and cytosol, respectively. GRTotal, GRα, and GRβ were also detected in amnion epithelial cells and chorionic epithelium of the fetal membranes, and the maternal endometrial epithelium. GRTotal and GRα were also present in amnion mesenchymal and glandular epithelium. GRTotal and GRα (95 kDa) protein levels were significantly (P < .05) higher during labor; GRβ (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.

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References

  1. Liggins GC, Fairclough RJ, Grieves SA, Kendall JZ, Knox BS. The mechanism of initiation of parturition in the ewe. Rec Prog Horm Res 1973;29:111–159.

    CAS  PubMed  Google Scholar 

  2. Challis JRG, Brooks AN. Maturation and activation of the hypothalamic-pituitary-adrenal function in fetal sheep. Endocr Rev 1989;10:182–204.

    Article  CAS  PubMed  Google Scholar 

  3. Challis JRG, Patrick JE, Cross J, Workewych J, Manchester E, Power S. Short-term fluctuations in the concentration of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids from sheep during late pregnancy. Can J Physiol Pharmacol 1981;59:261–267.

    Article  CAS  PubMed  Google Scholar 

  4. Fowden AL, Li J, Forhead AJ. Glucocorticoids and the preparation for life after birth: Are there long-term consequences of the life insurance? Proc Nutr Soc 1998;57:113–122.

    Article  CAS  PubMed  Google Scholar 

  5. Whittle WL, Patel FA, Alfaidy N, et al. Glucocorticoid regulation of human and ovine parturition: The relationship between fetal hypothalamic-pituitary-adrenal axis activation and intrauterine prostaglandin production. Biol Reprod 2001;64:1019–1032.

    Article  CAS  PubMed  Google Scholar 

  6. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988;240:889–895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Funder JW. Mineralocorticoids, glucocorticoids, receptors and response elements. Science 1993;259:1132–1133.

    Article  CAS  PubMed  Google Scholar 

  8. Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1985;318:635–641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Giguere V, Hollenberg SM, Rosenfeld MG, Evans RM. Functional domains of the human glucocorticoid receptor. Cell 1986;46:645–652.

    Article  CAS  PubMed  Google Scholar 

  10. Oakley RH, Sar M, Cidlowski JA. The human glucocorticoid receptor B isoform. Expression, biochemical properties, and putative function. J Biol Chem 1996;271:9550–9559.

    CAS  PubMed  Google Scholar 

  11. Oakley RH, Webster JC, Sar M, Parker CR Jr, Cidlowski JA. Expression and subcellular distribution of the beta-isoform of the human glucocorticoid receptor. Endocrinology 1997;138:5028–5038.

    Article  CAS  PubMed  Google Scholar 

  12. Heckt K, Carlstedt-Duke J, Stierna P, Gustafsson J, Bronnegard M, Wikstrom AC. Evidence that the β-isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. J Biol Chem 1997;272:26659–26664.

    Article  Google Scholar 

  13. Webster JC, Jewell CM, Sar M, Cidlowski JA. The glucocorticoid receptor: Maybe not all steroid receptors are nuclear. Endocrine 1994;2:967–969.

    CAS  Google Scholar 

  14. Pratt WB. The role of the heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 1993;268:21455–21458.

    CAS  PubMed  Google Scholar 

  15. Bamberger CM, Schulte HM, Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–261.

    Article  CAS  PubMed  Google Scholar 

  16. McKay LI, Cidlowski JA. Molecular control of immune/inflammatory responses: Interactions between nuclear factor-κB and steroid receptor-signaling pathways. Endocr Rev 1999;20:435–459.

    CAS  PubMed  Google Scholar 

  17. Hollenberg SM, Evans RM. Multiple and cooperative transactivation domains of the human glucocorticoid receptor. Cell 1988;55:899–906.

    Article  CAS  PubMed  Google Scholar 

  18. Yang K, Hammond GL, Challis JRG. Characterization of an ovine glucocorticoid receptor cDNA and developmental changes in its mRNA levels in the fetal sheep hypothalamus, pituitary gland and adrenal. J Mol Endocrinol 1992;8:173–180.

    Article  CAS  PubMed  Google Scholar 

  19. Yang K. Gene expression in the ovine fetus. J Reprod Fertil 1992;45(Suppl):85–95.

    CAS  Google Scholar 

  20. Gyomorey S, Lye SJ, Gibb W, Challis JRG. Fetal-to-maternal progression of prostaglandin H synthase-2 expression in ovine intrauterine tissues during the course of labor. Biol Reprod 2000;62:797–805.

    Article  CAS  PubMed  Google Scholar 

  21. Lye SJ, Dayes BA, Freitag CL, Brooks LJ, Casper RF. Failure of ritodrine to prevent preterm labor in the sheep. Am J Obstet Gyn 1992;167:1399–1408.

    Article  CAS  Google Scholar 

  22. Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.

    Article  CAS  PubMed  Google Scholar 

  23. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680–685.

    Article  CAS  PubMed  Google Scholar 

  24. Flint AP, Burton RD. Properties and ontogeny of the glucocorticoid receptor in the placenta and fetal lung of the sheep. J Endocrinol 1984;103:31–42.

    Article  CAS  PubMed  Google Scholar 

  25. Gyomorey S, Gupta S, Lye SJ, Gibb W, Labrie F, Challis JRG. Temporal expression of prostglandin H synthase type 2 (PGHS-2) and P450(C17)in ovine placentomes with the natural onset of labor. Placenta 2000;21:478–486.

    Article  CAS  PubMed  Google Scholar 

  26. Whittle WL, Holloway AC, Lye SJ, Gibb W, Challis JRG. Prostaglandin production at the onset of ovine parturition is regulated by both estrogen-independent and estrogen-dependent pathways. Endocrinology 2000;141:3783–3791.

    Article  CAS  PubMed  Google Scholar 

  27. Patel FA, Sun K, Challis JR. Local modulation by 11beta-hydroxysteroid dehydrogenase of glucocorticoid effects on the activity of 15-hydroxyprostaglandin dehydrogenase in human chorion and placental trophoblast cells. J Clin Endocrinol Metab 1999;84:395–400.

    CAS  PubMed  Google Scholar 

  28. Saoud CJ, Wood CE. Developmental changes and molecular weight of immunoreactive glucocorticoid receptor protein in the ovine fetal hypothalamus and pituitary. Biochem Biophys Res Commun 1996;229:916–921.

    Article  CAS  PubMed  Google Scholar 

  29. Sun M, Ramirez M, Challis JRG, Gibb W. Immunohistochemical localization of the glucocorticoid receptor in human cell membranes and decidua at term and preterm delivery. J Endocrinol 1996;149:243–248.

    Article  CAS  PubMed  Google Scholar 

  30. Whittle WL, Gibb W, Challis JR. The characterization of human amnion epithelial and mesenchymal cells: The cellular expression, activity and glucocorticoid regulation of prostaglandin output. Placenta 2000;21:394–401.

    Article  CAS  PubMed  Google Scholar 

  31. Economopoulos P, Sun M, Purgina B, Gibb W. Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the fibroblast cells in human amnion cultures. Mol Cell Endocrinol 1996;117:141–147.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. CIHR Institute of Human Development, Child and Youth Health, Departments of Physiology and Ob/Gyn, University of Toronto, Toronto, Canada

    Shalini Gupta MSc, Bsc, Sandor Gyomorey MSc, Stephen J. Lye PhD, William Gibb PhD & John R. G. Challis PhD

  2. Departments of Physiology and Ob/Gyn and Program in Development and Fetal Health, Samuel Lunenfeld Institute, MSH, Toronto, Canada

    Shalini Gupta MSc, Bsc, Sandor Gyomorey MSc, Stephen J. Lye PhD, William Gibb PhD & John R. G. Challis PhD

  3. Departments of Cellular and Molecular Medicine and Ob/Gyn, University of Ottawa, Ottawa, Canada

    Shalini Gupta MSc, Bsc, Sandor Gyomorey MSc, Stephen J. Lye PhD, William Gibb PhD & John R. G. Challis PhD

Authors
  1. Shalini Gupta MSc, Bsc
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  2. Sandor Gyomorey MSc
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  3. Stephen J. Lye PhD
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  4. William Gibb PhD
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  5. John R. G. Challis PhD
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Corresponding author

Correspondence to Shalini Gupta MSc, Bsc.

Additional information

We thank Dr. Mhoyra Frascr for her assistance preparing the fetal sheep.

This work was supported by CIHR, Institute of Human Development, Child and Youth Health (MOP-14097).

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Gupta, S., Gyomorey, S., Lye, S.J. et al. Effect of Labor on Glucocorticoid Receptor (GRTotal, GRα, and GRβ) Proteins in Ovine Intrauterine Tissues. Reprod. Sci. 10, 136–144 (2003). https://doi.org/10.1016/S1071-5576(03)00010-8

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  • DOI: https://doi.org/10.1016/S1071-5576(03)00010-8

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