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 (cGMP(ex)/cAMP (ex)) has been proposed as diagnostic tool in many forms of malignanci es. In vitro and in vivo studies have shown that sex steroids affect e xtracellular levels of cyclic nucleotides. Cyclic changes of these hor mones in premenopausal women may disturb the interpretation of the dia gnostic 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 determine d by RIA. Receptor status was evaluated by immunocytochemistry. Proges terone increased the cGMp(ex)/cAMP(ex) at all cell densities tested. T his effect resulted from increased cGMP and reduced cAMP extrusion. Es tradiol had no clear effect on cGMP(ex)/cAMP(ex), even when inhibition of cAMP extrusion was observed at low cell density. Receptors for ste roids were not detectable. Sex steroids interact with cyclic nucleotid es in C4-I cells in a non-genomic manner.