This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Johnson, R. F. Articles by Smith, R. Search for Related Content PubMed PubMed Citation Articles by Johnson, R. F. Articles by Smith, R. Related Collections Female Endocrinology

Expression of Glucocorticoid Receptor Messenger Ribonucleic Acid Transcripts in the Human Placenta at Term

Mothers and Babies Research Centre (R.F.J., N.R., V.M., T.Z., V.C., R.S.) and Department of Respiratory and Sleep Medicine (V.M.), Hunter Medical Research Institute, Newcastle, New South Wales, 2305 Australia; and Wellcome Trust Centre for Gene Regulation and Expression (R.F.J.), College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom

Address all correspondence and requests for reprints to: Dr. Renée Johnson, Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, University Walk, Clifton, Bristol BS8 1TD, United Kingdom. E-mail: Renee.Johnson{at}bristol.ac.uk.

Context: Differential promoter use and alternative splicing generate a variety of glucocorticoid receptor (GR) mRNA transcripts, potentially altering the cortisol responsiveness of gestational tissues during pregnancy and labor.

Objective: We examined GR mRNA transcript expression in term placentae before and after labor, in association with fetal sex and after glucocorticoid treatment.

Design: RNA from 34 placentae and from eight placental explants incubated with glucocorticoids were analyzed for the GR mRNA variants GR-, GR-β, GR-P, and GR- and the untranslated exon one variants 1A1, 1A2, 1A3, 1B, and 1C by quantitative RT-PCR.

Main Outcome Measure: mRNA expression was assessed.

Results: All GR mRNA variants examined were detected in the human placenta, with GR- and GR-1C mRNA having the highest expression of GR splice variants and exon 1 variants, respectively. GR-P mRNA abundance decreased with spontaneous labor (P < 0.01). GR-1A3 mRNA abundance changed with fetal sex, with a higher level in placentae of male fetuses (P < 0.05). GR-1C was the preferential promoter for GR-, GR-, and GR-P mRNA. GR-β mRNA was preferentially associated with GR-1A1. GR-P mRNA transcription switched to the GR-1A1 promoter after labor and to the GR-1A3 promoter in placentae from male fetuses. Glucocorticoid treatment significantly reduced transcription from promoters GR-1B and -1C and decreased GR- and GR-P mRNA abundance.

Conclusions: The human placenta expresses a variety of GR mRNA transcripts. GR- mRNA transcribed from the 1C promoter generates the majority of placental GR. However, alterations in promoter use and alternative splicing may modulate responses to cortisol during stressful events.