Human epithelial ovarian cancer cell steroid secretion and its control by gonadotropins

Abstract

To elucidate the role of gonadotropins in regulating steroid metabolism in human epithelial ovarian carcinoma (OV Ca), cells were cultured from a number of OV Ca localized to the ovary. These cells uniformly secreted 17-β-estradiol (E 2), and cells from some OV Ca also secreted progesterone (P), as well as CA 125. Secretion rates decreased with time in culture and number of subcultures. In the original and first few subcultures, 1–10 pg/ml/μg DNA/24 hr of E 2 was secreted and P secretion varied from 1 to 8 ng/ml/μg DNA/24 hr under basal conditions. Secretion rates for CA 125 were between 5 and 300 U/ml/day. Approximately 30% of the primary cultures from cystadenocarcinomas responded to hCG and hFSH and 70% of cultures responded to 8-Br-cAMP with 2- to 10-fold increases in secretion of E 2. In one primary culture, hCG produced a dose-related increase in E 2 production between 1 and 5 ng/ml, but the response declined to zero at 25 ng/ml. In the same cells, exposure to hCG and cAMP for 72 hr produced cell death, whereas hFSH had no such effect. Subculturing reduced steroidogenic responses to the hormones but the response to cAMP was maintained to a greater degree. These results suggest that some OV Ca-derived cells are steroidogenic in vitro and that some of these cells respond with increased E 2 secretion to agents which are well-known stimulators of steroidogenesis in normal ovarian cells.