Multidrug resistance phosphoglycoprotein (ABCB1) expression in the guinea pig placenta: developmental changes and regulation by betamethasone.
Placental ABCB1 plays an important role in fetal protection against xenobiotics in the maternal circulation. Limited evidence indicates that glucocorticoids regulate ABCB1 expression in other tissues. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids for threatened preterm labour, the effects of synthetic glucocorticoids on placental ABCB1 are important. We hypothesized that placental levels of ABCB1 are reduced in late gestation in the guinea pig and that synthetic glucocorticoids downregulate ABCB1 production. There was a significant decrease in placental Abcb1 mRNA expression in late gestation. Treatment of guinea pigs with betamethasone (1 mg/kg) on gestational days 40/41 and 50/51 resulted in a significant decrease in placental Abcb1 mRNA and protein expression. No sex differences were observed. Understanding the regulation of ABCB1 function will facilitate the development of treatment strategies for human fetal protection against maternally derived endobiotics and xenobiotics.
Kalabis
Grazyna M
GM
Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Petropoulos
Sophie
S
Gibb
William
W
Matthews
Stephen G
SG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology; D015262:Xenobiotics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D012333:RNA, Messenger; D015262:Xenobiotics; D001623:Betamethasone