INHIBITORY EFFECTS OF ESTROGEN, PROGESTERONE, ANDROGEN AND GLUCOCORTICOID ON DEATH OF NEONATAL MOUSE UTERINE EPITHELIAL-CELLS INDUCED TO PROLIFERATE BY ESTROGEN

Female newborn mice were given daily injections of estradiol-17beta (E2; 25 mug/mouse/day) for 4 days from the day of birth, and uterine cell death after this E2 priming was investigated by examining the apoptotic index (percentage of apoptotic cells), and the retention of H-3-radioactivity incorporated into epithelial or stromal DNAs after injection of [H-3]thymidine into the mice on the day after birth. With injections of vehicle only after E2 priming, the apoptotic index of the uterine epithelium increased markedly, being maximal on day 4 of injections, and the H-3-radioactivity retained in the epithelium decreased rapidly. Agarose gel electrophoresis of uterine epithelial DNAs on day 4 of injections showed a ladder pattern, characteristic of apoptotic cell death. However, daily injections of E2 (7.2 mug/g body wt) completely inhibited the increase in the apoptotic index and the loss of H-3-radioactivity in the epithelium. Daily injections of progesterone (80 mug/g body wt), 5alpha-dihydrotestosterone (DHT; 8 mug/g body wt), and dexamethasone (2 mug/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 H-3-radioactivity were found in the stroma for any treatment after E2 priming. The present results suggest that discontinuation of estrogen stimulation results in apoptotic cell death in the uterine epithelium of neonatal mice, but not in the stroma, and that estrogen, progesterone, DHT and dexamethasone inhibit cell death of uterine epithelium.