Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue.
BACKGROUND
The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel--alone and in combination with ethinyl estradiol--on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness.


METHODS
Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein.


RESULTS
A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use.


CONCLUSIONS
Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.
Ramakrishnan
Gopalakrishnan
G
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.
Rana
Anita
A
Das
Chandana
C
Chandra
Nimai Chand
NC
D045744:Cell Line, Tumor; D008078:Cholesterol, LDL / Q000378:metabolism; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D017135:Desogestrel / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D008078:Cholesterol, LDL; D003277:Contraceptives, Oral, Combined; D011973:Receptors, LDL; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel