Modulation of ectopic secretion of human chorionic gonadotropin by cultured ovarian adenocarcinoma cells

Modulation of ectopic human chorionic gonadotropin (hCG) secretion by a human nontrophoblastic ovarian papillary cystadenocarcinoma cell line maintained in monolayer culture was studied. Exposure of cells to methotrexate (MTX, 0.1 microM) significantly enhanced hormone secretion while actual cell replication was decreased. In contrast, exposure of cells to actinomycin D (25 pM) for 24 hr completely abolished hormone secretion and resulted in death of all cells. Exposure of the cells to hypothalamic peptides (thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin) did not alter hCG production. hCG secretion was stimulated after 24-hr incubation with dibutyryl cAMP (100 microM) and by prostaglandin F1 alpha (10 microM). Two separate mechanisms of modulation of ectopic hCG by these cells are possible: a cAMP-mediated stimulation independent of cell-growth kinetics after exposure to dibutyryl cAMP and prostaglandin F1 alpha, and a selective inhibition of DNA synthesis which results in slowing of cell replication and concomitant increase in hCG production per cell.