SITE AND MENSTRUAL CYCLE-DEPENDENT EXPRESSION OF PROTEINS OF THE TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR FAMILY, AND BCL-2 ONCOPROTEIN AND PHASE-SPECIFIC PRODUCTION OF TNF-ALPHA IN HUMAN ENDOMETRIUM

Apoptosis in human endometrial epithelium progressively increases from early to late secretory/menstrual phases and remains consistently mor e prominent in the basalis. It has been suggested that tumour necrosis factor (TNF) a secreted during the secretory/menstrual phases plays a role in induction of programmed cell death in these cells. In the pre sent study, we characterized expression of receptors of TNF alpha, Fas antigen and BCL-2 in endometrial cells to gain insight as to whether this type of cell death in endometrium may be related to differential or preferential expression of these proteins at specific phases of the menstrual cycle. In addition, to relate production of TNF alpha to th e development of apoptosis, the amount of TNF alpha released by human endometrium was measured. Immunostaining demonstrated that the TNF rec eptor (TNFr; p55/60)-I, TNFr-II (p75/80) as well as Fas protein were e xpressed in endometrial epithelium throughout the entire menstrual cyc le. This expression was progressively diminished from the basalis towa rds the upper functionalis. In the proliferative phase, the expression of BCL-2 was prominent in the endometrial glands particularly in thos e residing in the basalis. This expression became weak as early as the third post-ovulatory day and remained low during the remaining phases of the menstrual cycle. The amount of TNF alpha released by endometri al fragments obtained from various phases of the menstrual cycle was d etermined. The amount of TNF alpha released into the culture medium by the endometrium was low in the proliferative phase. However, the amou nt of released TNF alpha progressively increased in the secretory phas e and peaked in the menstrual phase. TNFr-I, TNFr-II, Fas, BCL-2 and T NF alpha could be identified by Western blot analysis of proteins extr acted from endometrium. Therefore, endometrial epithelium by virtue of expression of receptors of TNF alpha as well as Fas protein is proper ly poised to respond to ligand signals that regulate apoptosis. Induct ion of apoptosis in endometrial epithelium and menstrual shedding may be related to loss of the protective effect of BCL-2 as well as to the amount of TNF alpha.