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Retinoids and steroid hormones regulate differentiation of cultured human ectocervical cells

Gorodeski, George Israel
http://rave.ohiolink.edu/etdc/view?acc_num=case1054845951

Abstract Details

1990, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
The present study was predicated on the hypothesis that retinoids (analogues of vitamin A) have a direct effect on human female reproductive tract epithelia and that they modulate the effects of estradiol (E2) and progesterone (P) on these tissues. To study retinoid and steroid regulation of differentiation in vitro I used cultured ectocervical epithelial cells (ECE) grown on 3T3 monolayers. Confluent ECE cells free of non-epithelial cells as judged by lack of expression of vimentin, stratified spontaneously, terminally differentiated and formed cornified envelopes. The epithelial origin of these cells was determined by their morphology and the expression of protein and mRNA involucrin and cytokeratins. Differentiation of the ECE cells could be modulated in vitro by diethylstilbestrol (DES) and P and the cells expressed specific E2 binding sites (receptor). Four experiments were done: (1) Retinoids (Ro 13-6298, trans Retinoic Acid, Retinol) modulate differentiation of ECE cells in concentrations of 10-11M to 10-7M resulting in loss of stratification, suppression of envelopes (mainly Ro 13-6298) and increase in cell number (mainly Retinoic Acid). (2) Steroids, in concentrations of 10-11M to 10-6M also modulate differentiation: DES and Hydrocortisone (HC) increase while P and Testosterone suppress envelopes formation and HC increases cell number. Experiments using combinations of retinoids and steroids revealed that retinoids are more potent suppressors of envelopes than P, that DES and retinoids synergistically increase cell number and that DES renders the cells sensitive to P suppression of envelopes. (3) Changes in involucrin protein and mRNA are not the basis for envelopes regulation by retinoids and steroids. (4) Retinoids modulate cytokeratins expression: K13 (and mRNA) and K16 levels decrease and K19 (and mRNA) levels increase. Based on these results I conclude that in-vivo: (1) Vitamin A determines the basal degree of differentiation of ectocervical cells. (2) The sex steroid hormones regulate the state of differentiation of the ectocervical tissues around this set point. (3) Vitamin A regulates squamous metaplasia of the squamo-columnar junction by increasing the fraction of reserve cells. (4) Vitamin A maintains the upper reproductive tract epithelium in the form of simple columnar epithelium.
Richard Eckert (Advisor)
171 p.
Retinoids; steroid hormones; cultured; ectocervical cells

Recommended Citations

Citations

  • Gorodeski, G. I. (1990). Retinoids and steroid hormones regulate differentiation of cultured human ectocervical cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1054845951

    APA Style (7th edition)

  • Gorodeski, George. Retinoids and steroid hormones regulate differentiation of cultured human ectocervical cells. 1990. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1054845951.

    MLA Style (8th edition)

  • Gorodeski, George. "Retinoids and steroid hormones regulate differentiation of cultured human ectocervical cells." Doctoral dissertation, Case Western Reserve University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=case1054845951

    Chicago Manual of Style (17th edition)

case1054845951
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© 1990, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.