Regulation of Cholesterol and Progesterone Synthesis in Human Placental Cells in Culture by Serum Lipoproteins*

Abstract

Employing dispersed human trophoblastic cells in primary culture, the role of serum lipoproteins in regulating the synthesis of cholesterol and progesterone by the human placenta was investigated. The rate of secretion of progesterone by trophoblastic cells maintained in medium containing lipoprotein- poor serum was 100—190 ng mg⁻¹ cell protein, whereas progesterone secretion by cells maintained in medium containing low density lipoprotein (LDL) increased as a function of LDL concentration, reaching a rate of 390 ng mg⁻¹ cell protein 24 h⁻¹ at an LDL concentration of 420 μg protein/ml. The rate of progesterone secretion by trophoblastic cells maintained in media containing high density lipoprotein in various concentrations (0—1000 /xg protein/ml) was also investigated. At high density lipoprotein concentrations of 1000 ng/ml, the rate of progesterone secretion by the trophoblastic cells was half that attained by cells maintained in medium containing LDL. The rate of incorporation of [¹⁴C]acetate into cholesterol and progesterone by trophoblastic cells was examined to evaluate the effect of LDL on de novo synthesis of cholesterol. Trophoblastic cells maintained in medium containing lipoprotein-poor serum and no LDL incorporated acetate at a low rate (290 pmol mg⁻¹ cell protein 20 h⁻¹), whereas trophoblastic cells maintained in medium containing LDL (500 μg protein/ml) incorporated acetate at a rate of only 20 pmol mg⁻¹ cell protein 20 h⁻¹. We conclude that placental biosynthesis of progesterone is principally dependent upon cholesterol derived from maternal plasma LDL. (Endocrinology106: 1054, 1980)