Doctoral Dissertations

Date of Award

12-1997

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Comparative and Experimental Medicine

Major Professor

Linda Munson

Committee Members

Philip Bochsler, James Godkin, Joyce Merryman, Donald Torry

Abstract

Platelet-derived growth factor (PDGF) is a potent mitogenic polypeptide which has been implicated as a common pathway for numerous developmental, physiologic, and pathologic processes. Mediation of estrogenic activity in cyclic endometrial growth and pathologic endometrial proliferation is one of the potential roles of PDGF.

The possible role of PDGF as a mediator for estrogen driven endometrial proliferation was examined in culture and by tissue immunohistochemical methods. Treatment of cultured human endometrial epithelial cells (hEEC) with PDGF caused an increase in proliferation. Sequential exposure of the hEEC to the estrogen, diethylstilbestrol, and PDGF resulted in synergistic growth of the hEEC.

Immunohistochemical staining for PDGF receptors a and ẞ revealed immunoreactivity in human and murine endometrium which varied between tissue compartments with the stage of the estrous (menstrual) cycle. Proliferation of the endometrium was gauged by endometrial morphology and expression of the proliferating cell nuclear antigen (PCNA). A strong positive compartmental association between proliferation of glandular endometrial epithelium and the immunoreactivity for the PDGF receptors was found in both human and murine endometrium.

Endometrial proliferation in endometrial hyperplasia, endometrial adenocarcinoma and endometriosis may reflect proliferative pathways similar to the normal endometrium. Immunohistochemical examination of the endometrial epithelial component of specimens of these conditions revealed positive immunoreactivity for the PDGF receptors in the epithelium. Association of proliferation with expression of the PDGF receptors was limited to focal areas in these hyperproliferative conditions.

Endometriosis is an incompletely understood disorder of ectopic growth of endometrium in women and menstruating non-human primates. Peptide growth factors, including PDGF, have been suggested as mediators of endometriosis. An inexpensive, reliable animal model of endometriosis would aid in the investigation of this disease. An in vivo model, using human endometrial epithelial cells transplanted into the abdominal cavity of severe- combined-immuno-deficient (scid) mice, was developed and compared with the natural disease and existing models. Survival of the hEEC for up to 6 weeks, implant neovascularization, and hEEC recapitulation of rudimentary glandular structures, indicate the scid model is an excellent tool for further investigation of endometriosis and endometrial proliferative disorders.

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