Apolipoprotein E synthesis by cultured human ovarian granulosa cells: regulation by human chorionic gonadotropin and cholesterol

Abstract

Apolipoprotein E (Apo E) is a surface component of several classes of plasma lipoproteins and functions as a receptor ligand for the low-density lipoprotein (LDL) (B/E) receptor, the hepatic E receptor, and the LDL receptor related protein. In continuing studies of Apo E synthesis by extrahepatic steroidogenic tissue, we have examined Apo E production and its control in cultured human granulosa cells (GC). Human GC obtained at the time of oocyte aspiration for in vitro fertilization were cultured, and the following parameters were measured: progesterone secretion into the medium, Apo E synthesis and secretion, and Apo E messenger ribonucleic acid (mRNA) content of the GC. Human chorionic gonadotropin induces a decrease in Apo E protein synthesis and Apo E mRNA content. The addition of aminoglutethimide (which blocks cholesterol conversion to pregnenolone) and/or LDL (which provides the cell with cholesterol), both result in an increase in Apo E protein synthesis and Apo E mRNA content. These latter findings are in agreement with studies in nonsteroidogenic cells, which show that Apo E production is positively correlated with cell cholesterol content.