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J Clin Endocrinol Metab. 2008 Dec;93(12):4887-93. doi: 10.1210/jc.2008-1077. Epub 2008 Aug 26.

Expression of glucocorticoid receptor messenger ribonucleic acid transcripts in the human placenta at term.

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  • 1Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, 2305 Australia. Renee.Johnson@bristol.ac.uk

Abstract

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-alpha, GR-beta, GR-P, and GR-gamma 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-alpha 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-alpha, GR-gamma, and GR-P mRNA. GR-beta 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-alpha and GR-P mRNA abundance.

CONCLUSIONS:

The human placenta expresses a variety of GR mRNA transcripts. GR-alpha 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.

[PubMed - indexed for MEDLINE]
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