D Macinga | PubMed Health

PubMed1996

Relaxin modulates human cervical stromal cell activity.

The cervix undergoes profound changes in size and consistency during pregnancy which are designed to facilitate a normal delivery. These changes are under the control of a number of hormonal factors. Experimental and clinical studies suggest that relaxin, a protein hormone, plays a role in promoting cervical softening. One possible target site for the effects of relaxin on the cervix is the stroma. In the studies reported here, cultures of normal human cervical stromal cells were used to determine what direct relaxin has on cervical cells. Relaxin at concentrations ranging from 0.10-100 ng/mL had no effect on human cervical stromal cell proliferation, but was found to modulate stromal cell activity related to the remodeling of extracellular matrix. When gelatin substrate gels were used, relaxin stimulated the secretion of several cervical stromal proteinase activities, including 36,52, and 116 kDa. Inhibitor studies using ethylenediamine tetraacetate, 1,10-phenanthroline, and L-cysteine identify these gelatinases as metalloproteinases. Neither estradiol nor progesterone augmented the effects of relaxin. A relaxin-induced concentration-dependent increase in collagenase activity was observed when measured with a conventional collagen fibril assay. Finally, relaxin was found to increase glycosaminoglycan synthesis, as indicated by [3H]g-lycocyamine incorporation in human cervical stromal cell cultures. These results indicate the relaxin may regulate cervical ripening in humans, as it does in other species, by direct effects on cervical cells.

Cell Division↗

PubMedDate not supplied

Tamoxifen regulation of ectocervical cell differentiation.

OBJECTIVE: To determine the effects of tamoxifen on the growth and differentiation of normal human cervical cells and compare those effects with those of a synthetic estrogen, diethylstilbestrol (DES). In addition, the effects of these compounds on immortalized cervical cells and cervical tumor cells were ascertained. METHODS: Growth curves were used to determine the effects on cell proliferation. The expression of several proteins was used to determine the effects on cell differentiation. Binding assays and Western analysis were used to determine estrogen receptor levels. RESULTS: Both tamoxifen and DES inhibited the proliferation of normal cervical cells. This growth inhibition was coincident with an increase in cell differentiation as determined by cornified envelope formation. The increase in envelope number was not accompanied by an increase in involucrin or cornifin, two protein precursors of the envelope. The activity of transglutaminase, which enzymatically incorporates precursor proteins into the envelope, was not stimulated following treatment. Diethylstilbestrol did not alter the growth or differentiation of the human papillomavirus 16-immortalized cell line ECE16-1 or any of the cervical tumor cell lines. Of all the immortalized or cancer cell lines, only Caski cells were growth inhibited by tamoxifen. Normal ectocervical epithelial cells and Caski cells expressed the high-affinity 56-kDa estrogen receptor, but 3H-estradiol binding was not detected in cell extracts from either ME180 or ECE16-1 cells. Nevertheless, extracts from ME180 cells contained an immunoreactive band at the appropriate molecular weight for the estrogen receptor. CONCLUSIONS: These results suggest that tamoxifen and DES act similarly in normal cervical cells to promote cervical cell differentiation. However, because Caski cell growth was inhibited by tamoxifen and not DES, the effects of tamoxifen in these cells may be mediated by non-estrogen receptor mechanisms.

Cell Differentiation↗