CELLULAR-LOCALIZATION AND STEROID-HORMONE REGULATION OF MESSENGER-RNAENCODING TUMOR-NECROSIS-FACTOR RECEPTOR-I IN MOUSE UTERUS

Signals transduced by binding of tumour necrosis factor alpha (TNF) an d lymphotoxin alpha (LT-alpha) trimers to high-affinity cell membrane receptors, TNF-RI (p55/p60) and TNF-RII (p75/p80), affect many cell fu nctions. In this study, expression of the gene encoding TNF-RI in uter i of cyclic mice was mapped using in situ hybridization. TNF-RI hybrid ization signals fluctuated during the cycle. Signal intensity was high est during dioestrus-II, when mRNA encoding TNF-RI was present in endo metrial epithelial and stroma cells, as well as in myometrial smooth m uscle and connective tissue cells. The ability of oestradiol and proge sterone to modulate steady state concentrations of mRNA encoding TNF-R I in uterine cells was assessed by using in situ and northern blot hyb ridization procedures. Seven days after ovariectomy, low concentration s of mRNA encoding TNF-RI were detected by northern analysis and weak in situ hybridization signals were identified in epithelia and some my ometrial connective tissue cells. Administration of oestradiol, proges terone or oestradiol plus progesterone to ovariectomized animals stimu lated temporal and cell type-specific changes in steady state concentr ations of mRNA encoding TNF-RI that were unique to each hormonal regim en. Maximal induction of mRNA encoding TNF-RI required 24 h of oestrad iol stimulation and 72 h of progesterone stimulation. In uteri treated with oestradiol plus progesterone, the oestradiol pattern predominate d over the progesterone pattern. Thus, multiple cell types in cyclic m ouse uteri express the gene encoding TNF-RI, and expression in specifi c cells is controlled by female steroid hormones.