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


METHODS
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.


METHODS
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.
Johnson
Renée F
RF
Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, 2305 Australia. Renee.Johnson@bristol.ac.uk
Rennie
Natascha
N
Murphy
Vanessa
V
Zakar
Tamas
T
Clifton
Vicki
V
Smith
Roger
R
D000328:Adult; D017931:DNA Primers; D003627:Data Interpretation, Statistical; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007743:Labor, Obstetric / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D055815:Young Adult
D017931:DNA Primers; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid