Progesterone therapy results in partial reversibility of uterine abnormalities of the adult anovulatory rat

Abstract

The effects of progesterone therapy (5 mg, administered subcutaneously daily for 6 days) on the abnormal uterus of adult anovulatory Wistar rats have been studied. These rats, rendered anovulatory by neonatal treatment with testosterone propionate or clomiphene citrate, displayed severe hyperplasia and metaplasia of the uterine luminal epithelium and a disproportionately high content of nuclear oestrogen receptor, as a result of constant oestrogen stimulation unrelieved by progesterone [White, Moore, Elder & Lim (1981) Biochem. J. 196, 557-565]. Progesterone therapy resulted in the virtual elimination of the hyperplasia and metaplasia and a corresponding decrease in the content of nuclear oestrogen receptor with the proportion of the unoccupied nuclear receptor being increased to values exhibited by normal cyclic females. There was also a decrease in the content of progestin receptors, a putative index of oestrogenic stimulation. Further, in the testosterone-treated group, progesterone therapy resulted in the restoration of oestrogen receptor translocational responses to oestradiol stimulation. Progesterone treatment of these anovulatory rats thus provides a model system for investigating the biochemical mechanisms underlying progestin antagonism and regulation of oestrogen-stimulated cell proliferation.