DIFFERENTIAL EXPRESSION OF MEMBERS OF THE BCL-2 GENE FAMILY IN PROLIFERATIVE AND SECRETORY HUMAN ENDOMETRIUM - GLANDULAR EPITHELIAL-CELL APOPTOSIS IS ASSOCIATED WITH INCREASED EXPRESSION OF BAX

Glandular epithelial cells of the human endometrium initiate apoptosis in the secretory phase of the cycle. To better understand the regulat ion of apoptosis in this paradigm of endocrine-regulated cell turnover , Re studied the expression of the cell death regulatory genes, bax, b cl-2, and bcl-x, in human proliferative and secretory endometria relat ive to the absence or presence of apoptosis. As assessed by immunohist ochemistry, levels of BAX protein were modest in proliferative endomet rium and increased dramatically in the secretory phase when apoptosis was most prevalent. Expression of BAX was predominantly localized to e pithelial cells of the functionalis layer of the secretory endometrium . In contrast, BCL-2 immunoreactivity was maximal during the prolifera tive phase and decreased in the secretory phase. Moreover, BCL-2 was t opographically concentrated in the basalis layer. Immunoreactive BCL-X protein was observed mostly in glandular epithelial cells of the huma n endometrium. Compared with proliferative endometrium, secretory endo metrium showed stronger BCL-X staining, especially in the functionalis layer. By Western blotting we confirmed that both proliferative and s ecretory endometrium expressed the long or antiapoptosis form as well as the short or proapoptosis form of the BCL-X protein. Taken together , our results demonstrate a coordinated pattern of expression of bcl-2 gene family members in human endometrium during the menstrual cycle, with a shift toward greater levels of the proapoptosis protein, BAX, o ccurring in glandular epithelial cells during the secretory phase of t he cycle. Therefore, we conclude that cyclic changes in endometrial gr owth and regression may be precisely regulated by shifts in the ratio or balance of BCL-2 and related proteins in glandular epithelial cells .