Effects of Progestins and Glucocorticoids on Deoxyribonucleic Acid Synthesis in the Uterus of the Neonatal Mouse*

Abstract

The effects of progestins and glucocorticoids on cellular proliferation were examined in the uterus of 5-day-old mice by monitoring either the labeling index (LI) after exposure to [methyl-3H]thymidine ([3H]TdR) in vivo or the mitotic index (MI) after colchicine-induced arrest of cells in metaphase. In untreated 5-day-old mice, epithelial LI was 31%, and stromal LI was 15%. Eighteen hours after a single ip injection of 40 mg/kg progesterone, epithelial LI was reduced to 2.3% and remained low for 48 h. Stromal LI increased transiently, reaching a zenith (40%) 18 h after administration of progesterone and returning to control levels by 24 h. When mitotic activity was assessed 24 h after progesterone treatment, epithelial MI was decreased (control, 3.1%; progesterone, 0.23%) and stromal MI was increased (control, 0.60%; progesterone, 2.1%). Thus, the measured effects on LI were indicative of altered proliferative activity of the tissues. Glucocorticoids also inhibited epithelial LI, but had no effect on stromal LI. Eighteen hours after a single ip injection, dexamethasone inhibited epithelial LI to the same extent as progesterone treatment. Corticosterone did not significantly decrease epithelial LI, while cortisol produced an intermediate inhibitory response. To determine whether the high baseline LI in uterine epithelium of neonatal mice was estrogen dependent, uteri of 1-day-old mice were grafted under the kidney capsule of ovariectomized adult mice. Eight days later, the hosts were treated with either progesterone or vehicle and then killed 18 h later. After labeling the tissue with [methyl-3H]thymidine in vitro, the mean LI of the epithelium of the grafted uteri was 11.5%, while that of the vehicle-treated hosts was 0.10%. Progesterone treatment reduced the LI of the grafted uterine epithelium to 1.0%. These data demonstrate that uterine tissues of the neonatal mouse proliferate rapidly in the absence of gonadal steroids. Progestins and glucocorticoids specifically inhibit this estrogen-independent DNA synthesis of uterine epithelium.