Hormonal regulation of uterine epithelial cell proliferation. I. Effects of estradiol or progesterone administered separately.

Using an in vivo tritiated thymidine (3H-TdR) labeling followed by autoradiography, the effects at different times before sacrifice of single or paired injections of 17-beta-estradiol (E2) or progesterone (Pg) at various concentrations were investigated in adult B6D2FI ovariectomized mouse luminal and glandular uterine epithelium. With regard to the luminal epithelium, E2 (0.25, 2.50 or 25.00 micrograms/animal) exerts a mitogenic influence which is dose-related. Pg (125, 600 or 5000 micrograms/animal) exerts a significant proliferative effect only at a high dose. With regard to glandular epithelium, E2 and Pg have an almost identical mitogenic influence which is dose-related. A two-step Pg administration (2 x 125 micrograms) inhibits cell proliferation in glandular epithelium as compared to the promoting action exerted by a single injection. No refractory response was observed after a two-step E2 administration in either the luminal or the glandular epithelium. These data demonstrate that cell proliferation in the uterine luminal epithelium of an adult B6D2F1 mouse is very sensitive to E2 but not to Pg, whereas these two steroids have a similar mitogenic influence on the cell proliferation of the glandular epithelium. Moreover, a second Pg administration seems to have an inhibiting effect on cell proliferation as compared to that exerted by the first injection performed 12 or 24 hours earlier. In contrast, the repetition of E2 treatment would seem to exert an additive effect on uterine epithelial cell proliferation. In conclusion, epithelial components of the endometrium are complex steroid targets. The two major cell types (luminal, glandular) differ in their abilities to respond to steroid stimulation by entering into DNA synthesis.