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

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.

Effect of inhaled glucocorticoid treatment on placental 11beta-hydroxysteroid dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated by asthma.

BACKGROUND: Asthma is a common disease affecting 12% of Australian women with 55% of women experiencing at least one exacerbation during pregnancy. Exacerbations during pregnancy are associated with low birthweight neonates and stillbirth. One of the main reasons for maternal exacerbations during pregnancy is non-compliance with inhaled glucocorticoid treatment due to the misconception that inhaled glucocorticoids are harmful to the fetus. AIMS AND METHODS: We have therefore assessed whether the commonly used inhaled glucocorticoids reduce placental glucocorticoid metabolising capacity, by measuring 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) activity. As these treatments potentially increase the exposure of the fetus to the growth-inhibiting effects of glucocorticoids, we also examined the question of whether inhaled glucocorticoid use was associated with reduced birthweight. Pregnant women using budesonide (n = 18), fluticasone propionate alone (n = 14) and fluticasone propionate in combination with the long-acting beta2 agonist salmeterol (n = 9) were compared to a non-asthmatic control group (n = 20). RESULTS: The use of inhaled budesonide was associated with significantly increased placental 11beta-HSD-2 activity relative to the control group. Inhaled glucocorticoid use for the treatment of asthma was associated with normal birthweight. In the small number of women using combination therapy (fluticasone and salmeterol), there was reduced birthweight compared to the control group. CONCLUSION: Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.