Inhibitory effects of estrogen, progesterone, androgen and glucocorticoid on death of neonatal mouse uterine epithelial cells induced to proliferate by estrogen

Abstract

Female newborn mice were given daily injections of estradiol-17β (E 2; 25 μg/mouse/day) for 4 days from the day of birth, and uterine cell death after this E 2 priming was investigated by examining the apoptotic index (percentage of apoptotic cells), and the retention of 3H-radioactivity incorporated into epithelial or stromal DNAs after injection of [ 3H]thymidine into the mice on the day after birth. With injections of vehicle only after E 2 priming, the apoptotic index of the uterine epithelium increased markedly, being maximal on day 4 of injections, and the 3H-radioactivity retained in the epithelium decreased rapidly. Agarose gel electrophoresis of uterine epithelial DNAs on day 4 of injections showed a ladder pattern, characteristics of apoptotic cell death. However, daily injections of E 2 (7.2 μg/g body wt) completely inhibited the increase in the apoptotic index and the loss of 3H-radioactivity in the epithelium. Daily injections of progesterone (80 μg/g body wt), 5α-dihydrotesterone (DHT; 8 μg/g body wt), and dexamethasone (2 μg/g body wt) also inhibited both parameters, although not completely. The inhibitory effects of DHT and progesterone were abolished by the antiandrogen, flutamide and antiprogesterone, RU 486, respectively. In contrast, no apoptotic cells and no loss of 3H-radioactivity were found in the stroma for any treatment after E 2 priming. The present results suggest that discontinuation of estrogen stimulation results in apoptotic cell death in the uterine epithelium of neonatal mice, but not inthe stroma, and that estrogen, progesterone, DHT and dexamethasone inhibit cell death of uterine epithelium.