Content of gonadotropins in cultured human malignant cells and effects of sodium butyrate treatment on gonadotropin secretion by HeLa cells.

Twenty-one of 82 human cell lines examined for production of human chorionic gonadotropin and its subunits (HCG-alpha and HCG-beta) produced either one or both subunits at some phase in their growth. Of these, 14 produced an excess amount of free alpha subunit, and seven produced HCG-beta or complete HCG without evidence for free alpha subunit synthesis. Five of the HCG-producing cell lines also contained or secreted the beta subunit of human luteinizing hormone. CBT cells derived from a glioblastoma multiforme and JAR choriocarcinoma cells secreted significant amounts of the beta subunit of human luteinizing hormone, while three other cell lines (breast carcinoma MCF-7, HeLa S3, and melanoma A375) produced small amounts of the beta subunit of human luteinizing hormone but did not appear to secrete it. Two cell lines (the melanoma line A375 and the SV40-transformed line SV80) appeared to contain small amounts of human follicle-stimulating hormone. Sodium butyrate caused a 40-fold induction in the secretion of both HCG-alpha and HCG-beta by HeLa S3 cells, but the total amount of HCG-alpha secretion induced was 800-fold greater than that of HCG-beta. Induction was blocked by actinomycin D (1 microgram/ml) and cycloheximide (5 microgram/ml) but was not affected by 1-beta-D-arabinofuranosylcytosine at a concentration (5 microgram/ml) that blocked DNA synthesis 99%. These results indicate that a number of malignant human cell lines produce the subunits of both placental and pituitary gonadotropins and that there is frequently an excess secretion of the free alpha subunit common to these hormones.