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-α, GR-β, GR-P, and GR-γ 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-α 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-α, GR-γ, 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-α and GR-P mRNA abundance.Conclusions:
The human placenta expresses a variety of GR mRNA transcripts. GR-α 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.