Effects of progesterone on prostaglandin E2-induced changes in glycosaminoglycan synthesis by human cervical fibroblasts in culture

Prostaglandins are known to induce cervical ripening and this effect may be mediated by an increase in glycosaminoglycan (GAG) concentration. The aim of this study was to assess the effects of progesterone on prostaglandin E-2 (PGE(2))-induced changes in GAG synthesis by human cervical cells in culture. Human cervical fibroblasts were obtained by cervical biopsies in hormonally active women and cultured. Cells were submitted to an incubation with progesterone or control medium. A second incubation was then performed with increasing concentrations of PGE(2). GAG synthesis by the cervical cells was assayed after extraction, by incorporation of [H-3]-glucosamine and [S-35]-sulphate into GAGs. It was found that progesterone alone induced a dose-dependent increase in GAG synthesis. After pre-incubation with progesterone, PGE(2) further increased [H-3]-glucosamine and [S-35]-sulphate uptake. However, when expressed as percentage of stimulation, the stimulatory effect of PGE(2) on GAG synthesis was inhibited at high progesterone concentrations. Therefore we concluded that, although high concentrations of progesterone increase the overall synthesis of GAG, they may also play a preventative role against PGE(2)-induced changes in GAG production during pregnancy.