Effect of a combination oral contraceptive (desogestrel+ethinyl estradiol) on the expression of low-density lipoprotein receptor and its transcription factor (SREBP2) in placental trophoblast cells

Abstract: Background: This in vitro study deals with the effect of a combination oral contraceptive steroid — desogestrel and ethinyl estradiol — on the expression of low-density lipoprotein receptor (LDLR) and its transcription factor (SREBP2) in assessing the functional effectiveness of the LDLR. Study design: Differentiated primary placental trophoblast cells isolated from term human placentae and cells from Jar cell line were used for the study. Low-density lipoprotein receptor and SREBP2 expressions were assessed by immunocytochemistry and immunoblot assays with and without combination contraceptive steroid challenge. Functional activity of LDLR was studied by rating the profile of cellular uptake of fluorescent Dil-LDL (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanin perchlorate-LDL). Quantitation of Dil-LDL was done spectrofluorometrically. Results: Variation of concentration(s) of either of the components of a combination preparation (desogestrel and ethinyl estradiol) showed a comparable change in the expressions of LDLR and SREBP2 to attain their optimal levels. Maximum expression and a significant functional effectiveness were observed at a unique combination of desogestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL). Conclusion: The stimulatory effect of a combination contraceptive steroid on LDLR expression is an associated phenomenon of the contraceptive-mediated stimulation of SREBP2 expression. [Copyright &y& Elsevier]