To examine more closely the anti-oestrogenic action of progesterone (P), its effect on various parameters in the 17 fl-oestradiol (E2)-primed uterus of the mouse, guinea pig, rabbit and ewe was studied. Changes in uterine wet weight, rate of in vitro protein synthesis, protein: DNA and RNA :. DNA ratios, peroxidase activity and the level of cytosol receptors for E2 and P were measured. Considerable between-species differences in the effect of P on these parameters were observed. The anti-uterotrophic action was greater in the mouse than in the guinea pig and was not seen in the rabbit or ewe. P inhibited protein synthesis in the mouse, was without significant effect in the guinea pig and was mildly stimulatory in the rabbit and ewe. Inhibitory effects on protein: DNA and RNA: DNA ratios were substantial in the mouse, minor in the guinea pig and absent in the rabbit and ewe. Peroxidase activity was decreased in the mouse and guinea pig, essentially lacking in the rabbit and not detectable in the ewe. In all species the level of both oestrogen and progesterone cytosol receptors was decreased, although the effect on the E2 receptor was less marked in the ewe.The results indicate that in the species studied an effect of P on the replenishment of the E2 receptor is not necessarily associated with other anti-oestrogenic actions of P and argue against the concept that initial anti-oestrogenic actions of P are mediated via a specific effect on such replenishment.
IntroductionIn the ovariectomized rat or mouse progesterone (P) substantially inhibits the rapid increases in RNA and protein accumulation and uterine weight that are seen in animals receiving large doses of oestrogen only (Roberts and Szego 1953;Martin 1963;Miller and Emmens 1969;Miller 1978). P also diminishes the cytosol concentration of specific, high-affinity 17 p-oestradiol (E 2 ) receptor in the uterus of these species, and several authors have suggested that the anti-oestrogenic or anti-uterotrophic activity of P may be mediated by this particular action of P on the E2 receptor (Bhakoo and Katzenellenbogen 1977;Clark et al. 1977;Coulson and Pavlik 1977).When ovariectomized ewes receive P together with large doses of E2 the P does not interfere with oestrogen-induced increases in uterine weight and endometrial RNA: DNA ratios (Miller 1976;Miller et al. 1977a). In these studies P caused only a small decrease in the cytosol concentration of E2 receptor in whole uterus. Because of these findings, we suggested that the apparent inability of P to much reduce the uterine level of E2 receptor in the ewe may explain the absence of other anti-oestrogenic actions of P in this species.