Effects of progesterone plus estradiol on vaginal epithelium showing estrogen-independent proliferation and cornification in neonatally estrogenized and androgenized mice.

Abstract

Studies were undertaken to investigate vaginal response to progesterone plus estradiol in neonatally estrogenized or androgenized, ovariectomized adult mice showing estrogen-independent persistent alterations in the vaginal epithelium. Group 1 of C57BL/Tw strain mice were controls receiving only the oil vehicle. For 5 days from day of birth, Group 2 was given sc injections of 50 mcg of estradiol-17beta (E2) and Group 3 was given 100 mcg of 5alpha-dihydrotestosterone (DHT). All mice were ovariectomized at 10 days of age. 10 animals of each group were sacrificed at 60 days of age (Groups 1a, 2a, and 3a). 10 other animals in each group were given daily sc injections of 2 mg of progesterone plus .01 mcg of E2 for 5 consecutive days beginning at 60 days of age; they were killed on the day following the last injection (Groups 1b, 2b, and 3b). Vaginas were removed for examination. In the 60-day-old ovariectomized control group, the vagina epithelium was atrophic. In mice given E2 or DHT neonatially (Groups 2a and 2b) the epithelium was markedly proliferated. Superficial layers of the epithelium were undergoing cornification or parakeratosis in some areas in all E2-treated and in 5 of 10 DHT-treated mice. The remaining 5 androgenized mice had both mucified and cornified areas of the superficial epithelium. In mice given DHT neonatally, vaginal cornification varied with the age at ovariectomy. The presence of the ovaries for a longer period enhanced proliferation and cornification. Findings appear to indicate that, except in the fornico-cervical region, the response of epithelial cells to progesterone plus E2 was markedly affected by neonatal injections of E2 or DHT. The changes induced by neonatal injections of E2 or DHT.