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Placental P-glycoprotein is unaffected by timing of antenatal glucocorticoid therapy but reduced in SGA preterm infants.


Placenta. 2013 Feb 18;


Authors: Hodyl NA, Stark MJ, Butler M, Clifton VL


Abstract

INTRODUCTION: The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of glucocorticoid metabolising enzymes, such as 11 beta hydroxysteroid dehydrogenase (11βHSD), and proteins that efflux glucocorticoids, such as P-glycoprotein (P-gp). We have shown that 11βHSD2 activity is responsive to antenatal glucocorticoids, however the effect on placental P-gp remains unknown. Since antenatal glucocorticoids have a greater prophylactic effect in females compared to males, we also assessed whether this therapy induced sexually dimorphic effects on P-gp expression, as well as on placental inflammatory processes mediated by corticosteroids. METHODS: Placentas were collected from 53 women presenting in threatened preterm labour, and processed to assess cytokine and P-gp mRNA expression, as well as P-gp localisation using immunohistochemistry. RESULTS: Placental cytokine, P-gp mRNA and protein expression were not altered by timing of antenatal glucocorticoids or fetal sex. However, both P-gp mRNA and protein expression were significantly reduced in placentas from infants born small for gestational age (SGA) compared to appropriately grown infants (p < 0.05), suggesting a role for P-gp in its pathogenesis via the provision of a net increase in fetal exposure to bioactive exogenous glucocorticoids. CONCLUSIONS: While this study identified no change in placental P-gp following antenatal glucocorticoids, it has provided evidence that P-gp plays an important role in cases of SGA. This supports the known mechanistic relationship between antenatal glucocorticoids, fetal development and the postnatal phenotype. Given that P-gp also confers fetal protection from a number of drugs, this finding warrants further investigation to improve clinical management of the SGA fetus.

PMID: 23425635 [PubMed - as supplied by publisher]