Hormonal regulation and expression of the jun-D protooncogene in specific cell types of the rat uterus

Abstract

Steroid hormone regulation and cell-type specific expression of the jun-D protooncogene in rat uterus was examined. Adult, ovariectomized rats were injected with progesterone, testosterone, 17β-estradiol (E 2-17β), 16α-estradiol (E 2-16α), dexamethasone or cycloheximide. Uteri were collected between 0 and 6 h post-treatment. Northern blot analysis of uterine RNA revealed that induction of jun-D was specific for estrogenic steroids, as progesterone and testosterone had no effect on expression of this member of the jun gene family. Treatment with E 2-17β increased jun-D mRNA levels by approx. 5-fold, with expression reaching peak levels at 3 h after treatment and declining thereafter. Administration of E 2-16α, a short-acting estrogen that does not cause uterine cell proliferation, increased expression of jun-D but with different kinetics compared to the long-acting E 2-17β. The mRNA levels of jun-D increased by 3-fold 1 h after administration of E 2-16α but declined soon after. Slight induction of jun-D mRNA by dexamethasone was apparent, but to a much lesser extent compared to estrogen. The protein synthesis inhibitor, cycloheximide, did not block jun-D induction, indicating that this is an “immediate early” response. Expression of Jun-D protein was examined by immunohistochemical methods. E 2-17β treatment activated jun-D primarily in the nuclei of luminal and glandular epithelial cells of the endometrium. These results demonstrate that hormonal induction of jun-D is specific for estrogens and that uterine expression of this protooncogene occurs in a cell-type specific manner.