Modulation of endocrine and transport functions in human trophoblasts by saquinavir and nelfinavir.
OBJECTIVE
The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus.


METHODS
The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality.


RESULTS
Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1.


CONCLUSIONS
These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions.
Beghin
Delphine
D
Univ Paris-Sud, EA 2706, IFR141, Faculté de Pharmacie, Châtenay- Malabry, France. delphinebeghin@free.fr
Forestier
François
F
Noël-Hudson
Marie-Sophie
MS
Gavard
Laurent
L
Guibourdenche
Jean
J
Farinotti
Robert
R
Gil
Sophie
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D015726:Giant Cells / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D033261:Maternal-Fetal Relations / Q000187:drug effects*; D019888:Nelfinavir / Q000494:pharmacology*; D011247:Pregnancy; D019258:Saquinavir / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051242:Caveolin 1; D006063:Chorionic Gonadotropin; D017320:HIV Protease Inhibitors; D019888:Nelfinavir; D019258:Saquinavir