HUMAN ENDOMETRIAL TRANSFORMING GROWTH-FACTOR-ALPHA - A TRANSMEMBRANE,SURFACE EPITHELIAL PROTEIN THAT TRANSIENTLY DISAPPEARS DURING THE MIDSECRETORY PHASE OF THE MENSTRUAL-CYCLE

OBJECTIVE: To characterize the forms of transforming growth factor-alp ha (TGF-alpha) in normal human endometrium, to evaluate the regional a nd temporal changes in TGF-alpha expression, and to correlate the patt ern of TGF-alpha expression with physiologic events in the endometrium . METHODS: Immunohistochemistry and Western blot analyses were perform ed using two TGF-alpha antisera, one raised against the active extrace llular N-terminus and the other recognizing the intracellular carboxy terminus of the protein. Immunohistochemistry was performed on hystere ctomy specimens from premenopausal women with normal menstrual cycles. Soluble and membrane-bound endometrial proteins were isolated from fr esh tissue for Western blot analysis. RESULTS: Antibodies recognizing the intracellular and extracellular domains of TGF-alpha exhibited ide ntical immunohistochemical staining patterns. Transforming growth fact or-alpha localized primarily to endometrial epithelial cells, and the most intense staining was in the luminal surface epithelium. In the su rface epithelium, TGF-alpha staining was intense in the proliferative phase, decreased during the early secretory phase, was at its nadir in the midsecretory phase, and rebounded in the late secretory phase. We stern blot analysis demonstrated two transmembrane forms. The 28-kD pr otein contained both intracellular and extracellular antigens, and the 18-kD protein contained only the intracellular antigen. CONCLUSION: W estern blot data were consistent with the hypothesis that the extracel lular segment of TGF-alpha is cleaved from the transmembrane precursor in vivo, as has been demonstrated in other tissues. Immunohistochemis try demonstrated that the TGF-alpha antigens are concentrated in the l uminal surface epithelium and decline and disappear in the early to mi dsecretory phase. These findings suggest that the most active period o f membrane-bound TGF-alpha cleavage corresponds with the interval duri ng which preimplantation embryos are in the uterine cavity. Copyright (C) 1997 by the Society for Gynecologic Investigation.