Serum modifies the concentration-dependent effects that sex steroids exert on cgmp and cAMP levels, and the growth of human c4-I cells (carcinoma of the uterine cervix).

About 50% of the cases with invasive carcinoma of the uterine cervix occurs before menopause. Cyclic changes of sex steroids may therefore interfere with the ratio between extracellular levels of cGMP and cAMP (cGMP(ex)/cAMP(ex)). This ratio has been proposed as a diagnostic marker of malignant diseases. In the present study, we tested the ability of sex steroids to affect cAMP and cGMP levels after 96 h exposure, in an established in vitro model of carcinoma of the uterine cervix (C4-I cells). Serum may modify the effects of sex steroids, and due to this, the present experiments were performed both in a chemically defined medium (CDM) and a serum-supplemented medium (SSM). Testosterone caused a concentration-dependent increase of cGMP(ex)/cAMP(ex) in SSM. Progesterone caused a concentration-dependent inhibition of cell growth in SSM and a decrease in cGMP(ex)/cAMP(ex). Progesterone had noed a concentration-dependent increase in cGMP(ex)/cAMP(ex). No distinct effects on, were seen in the other situations. The present study demonstrates that steroids affect the distribution of cGMP and cAMP to the extracellular compartment, and that serum modifies these effects.