MOUSE ENDOMETRIAL TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RIBONUCLEIC-ACID AND PROTEIN - LOCALIZATION AND REGULATION BY ESTRADIOL AND PROGESTERONE

Tumor necrosis factor-alpha (TNF) messenger RNA (mRNA) and protein hav e been identified in the uteri of cycling rats, mice, and women. In th is study, a mouse model was used to investigate the cell-specific expr ession and regulation of the TNF gene in the endometrium. Uteri from c ycling and ovariectomized hormone-reconstituted mice were tested by in situ and Northern blot hybridizations as well as by immunohistochemis try. Cyclic variations were observed in TNF mRNA. Although weak to und etectable during proestrus, estrus, and diestrus-I, TNF mRNA was prese nt in both epithelial and stromal cells on diestrus-II. TNF protein wa s observed in the endometrium on each day of the estrous cycle, primar ily in the epithelial cells. Stromal TNF immunoreactivity was observed only during diestous-I. Seven days after ovariectomy, TNF mRNA and pr otein were undetectable in the endometrium. Specific message and prote in were restored in both epithelial and stromal cells after administra tion of 17 beta-estradiol (E(2)), progesterone (P-4) and E(2) plus P-4 . E(2) treatment resulted in a biphasic pattern of TNF mRNA expression , mRNA was present in epithelial cells 1 and 6 h posttreatment, was no t detectable after 24 h, and then was present in both the epithelium a nd stroma after 72 h. In contrast, TNF mRNA was detectable at all time points after P-4 administration. TNF mRNA was localized to both the e pithelium and stroma until 72 h of P-4 treatment, when stromal TNF mRN A was no longer detectable. TNF mRNA was also present at all time poin ts examined after the combination E(2) and P-4 treatment. TNF mRNA was invariably localized to the epithelium; however, stromal mRNA fluctua ted over the course of treatment. TNF mRNA was in the stroma 1 and 24 h post-E(2) plus P-4 treatment, but was not present at the 6 and 72 h points. In general, the pattern of TNF protein matched that of the TNF mRNA, with a few exceptions. Twenty-four hours after E(1) treatment, TNF mRNA was not detectable; however, TNF protein was present in the e pithelium. The opposite was observed 24 h after E(2) plus P4 administr ation when the epithelium and stroma contained TNF mRNA; however, no p rotein was observed. In addition, with the exception of 72 h of P-4 tr eatment, stromal TNF protein was not abundant, although TNF mRNA was o ften detected. In summary, the results of this study indicate that bot h epithelial and stromal cells contain TNF mRNA and protein and that E (2) and P-4 exert individual influences on the cell-specific expressio n of TNF transcripts and protein.