Progesterone and beta-estradiol influence the cell density-dependent distribution of cyclic nucleotides across the cell membrane of human C4-I cells (squamous carcinoma of the uterine cervix) by a non-genomic mechanism.

The ratio between extracellular levels of cGMP and cAMP (cGMPex/cAMPex) has been proposed as diagnostic tool in many forms of malignancies. In vitro and in vivo studies have shown that sex steroids effect extracellular levels of cyclic nucleotides. Cyclic changes of these hormones in premenopausal women may disturb the interpretation of the diagnostic marker. C4-I cells grew in the presence of beta-estradiol and progesterone in a chemically defined medium. Cells were sampled during the logarithmic growth phase. Cyclic nucleotide levels were determined by RIA. Receptor status was evaluated by immunocytochemistry. Progesterone increased the cGMPex/cAMPex at all cell densities tested. This effect resulted from increased cGMP and reduced cAMP extrusion. Estradiol had no clear effect on cGMPex/cAMPex even when inhibition of cAMP extrusion was observed at low cell density. Receptors for steroids were not detectable. Sex steroids interact with cyclic nucleotides in C4-I cells in a non-genomic manner.