Regulation of human placental trophoblast low-density lipoprotein uptake in vitro by estrogen.

In the present study, human trophoblast cells were studied in culture to determine the effect of estrogen on low-density lipoprotein (LDL) uptake and progesterone formation. Cytotrophoblasts were obtained from term human placentas and incubated for 72 h with 10% FBS to stimulate formation of syncytia. Syncytiotrophoblasts were then incubated for an additional 48 h with estradiol and/or LDL protein. Estradiol plus LDL stimulated progesterone to a level that was 133% greater (P < 0.05) than control (314 +/- 69 ng/mg protein) or LDL alone, suggesting that estrogen stimulated progesterone formation via an increase in LDL uptake and utilization. To examine this possibility, trophoblast cells were cultured with estradiol for 48 h as above, then incubated for 12 h with 6-200 micrograms/mL [125I]LDL. Mean (+/- SE) specific uptake of [125I]LDL (ng/mg cell protein) was approximately 50% greater (P < 0.01) with estradiol (638 +/- 23) than with vehicle (429 +/- 54). Scatchard analysis demonstrated that the dissociation constant for LDL uptake was similar in the presence (2.9 +/- 0.4 x 10(-6)M) and absence (2.8 +/- 0.6 x 10(-8)M) of estradiol, indicating that estrogen increased LDL receptor number without affecting affinity. LDL uptake was increased (P < 0.05) by incubating trophoblast with as little as 0.10 ng/mL estradiol (approximately 10(-9) M). We conclude that estrogen regulates placental trophoblast cell uptake of LDL and, thus, the availability of cholesterol for progesterone bio-synthesis during human pregnancy.