HORMONAL-REGULATION AND EXPRESSION OF THE JUN-D PROTOONCOGENE IN SPECIFIC CELL-TYPES OF THE RAT UTERUS

Steroid hormone regulation and cell-type specific expression of the ju n-D protooncogene in rat uterus was examined. Adult, ovariectomized ra ts were injected with progesterone, testosterone, 17beta-estradiol (E2 -17beta), 16alpha-estradiol (E2-16alpha), dexamethasone or cycloheximi de. Uteri were collected between 0 and 6 h post-treatment. Northern bl ot analysis of uterine RNA revealed that induction of jun-D was specif ic for estrogenic steroids, as progesterone and testosterone had no ef fect on expression of this member of the jun gene family. Treatment wi th E2-17beta increased jun-D mRNA levels by approx. 5-fold, with expre ssion reaching peak levels at 3 h after treatment and declining therea fter. Administration of E2-16alpha, a short-acting estrogen that does not cause uterine cell proliferation, increased expression of jun-D bu t with different kinetics compared to the long-acting E2-17beta. The m RNA levels of jun-D increased by 3-fold 1 h after administration of E2 -16alpha but declined soon after. Slight induction of jun-D mRNA by de xamethasone was apparent, but to a much lesser extent compared to estr ogen. The protein synthesis inhibitor, cycloheximide, did not block ju n-D induction, indicating that this is an ''immediate early'' response . Expression of Jun-D protein was examined by immunohistochemical meth ods. E2-17beta treatment activated jun-D primarily in the nuclei of lu minal and glandular epithelial cells of the endometrium. These results demonstrate that hormonal induction of jun-D is specific for estrogen s and that uterine expression of this protooncogene occurs in a cell-t ype specific manner.