RAPID NON-GENOMIC AND CONCENTRATION-DEPENDENT EFFECTS OF PROGESTERONEIN C4-I CELLS ON THE PROPOSED TUMOR-MARKER - RATIO BETWEEN EXTRACELLULAR CGMP AND CAMP LEVELS

The extracellular cGMP levels or the ratio between extracellular level s of cGMP and cAMP (cGMP(ex)/cAMP(ex)) have been proposed as tumor mar ker for premalignant and malignant diseases of the uterine cervix. Mor e than 50% of cervical cancers occur in premenopausal women and detail ed information about hormonal and drug effects on the extracellular le vels of cyclic nucleotides is of importance. In the present study we h ave investigated the effect of progesterone (0.1-100 mu M), theophylli ne (1-1000 mu M), probenecid (0.1-100 mu M) and verapamil (0.1-100 mu M) on cGMP(ex)/cAMP(ex) of C4-I cells (a human cell line derived from a squamous carcinoma of the uterine cervix). Within 30 min progesteron e caused a concentration-dependent elevation of cGMP(ex)/cAMP(ex), whe reas the other compounds had no marked effect. Identical results were obtained for C4-I cells in monolayer and in suspension. The effects we re explained by the observation that progesterone stimulated cGMP effl ux, but inhibited the cAMP efflux. The other compounds inhibited the e xport of both nucleotides to a similar degree. The present data sugges t that progesterone affects the export of cyclic nucleotides in non-ge nomic manner and may hamper the interpretation of cGMP(ex)/cAMP(ex) in the luteal phase in premenopausal women with cancer of the uterine ce rvix.