MODIFICATION BY PROGESTERONE OF OESTRADIOL-INDUCED CELL PROLIFERATION, RNA SYNTHESIS AND OESTRADIOL DISTRIBUTION IN THE RAT UTERUS

Summary. Progesterone pretreatment (5 mg/day) of ovariectomized— adrenalectomized rats for at least 12 hr abolished the response of the uterine luminal epithelium to oestradiol (0·2 μg) with respect to (i) mitotic activity, (ii) nucleolar enlargement, and (iii) [3H]uridine uptake, and suppressed the uptake of [3H]oestradiol by the epithelial cells, as judged by dry-mount autoradiography. Progesterone pretreatment for periods exceeding 36 hr redirected the mitogenic action of oestradiol and its stimulatory action on [3H]uridine uptake from the epithelium to subepithelial stromal cells. The latter are not responsive to the action of oestradiol on its own. High resolution (EM) autoradiography revealed preferential accumulation of [3H]uridine over the stromal nucleoli, supporting the view that the bulk of the RNA synthesized as an early response to oestradiol is ribosomal precursor RNA. In the glandular epithelium, progesterone prevented the induction of mitotic activity, but not the stimulation of [3H]uridine uptake, by oestradiol; the ability to accumulate [3H]oestradiol remained unaffected. Rats injected with oestradiol during delayed implantation showed a mitotic response in the stroma, but not in the luminal or glandular epithelium, and failed to accumulate [3H]oestradiol in the luminal epithelium. In pregnant and pseudopregnant rats, mitotic activity declined sharply in epithelial and glandular cells after Day 2 post coitum. This was followed by a sharp rise in the rate of thymidine incorporation and cell division of the subepithelial stromal cells. The reciprocal changes in these tissues, previously described in the pregnant mouse, are ascribed to an interaction between progesterone and oestradiol. It is inferred that significant oestrogen secretion commences late on Day 2 post coitum, i.e. well before the time postulated for the preimplantation `oestrogen surge.' The rate of DNA synthesis in pseudopregnant rats reached a peak on Day 5 post coitum, coinciding with maximal uterine sensitivity to deciduoma-inducing stimuli, but mitotic rate in both pregnant and pseudopregnant rats declined sharply before the morning of Day 5, suggesting a prolongation of the G2 phase of the mitotic cycle at that time.