Effects of Progesterone on the Oestrogen-Stimulated Uterus: a Comparative Study of the Mouse, Guinea Pig, Rabbit and Sheep

Abstract

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.

Uterine and Placental Growth: RNA and Protein Metabolism and Steroid Hormone Receptor Levels in the Endometrium, Whole Uterus and Cotyledons during Pregnancy in the Ewe

“…In non-pregnant, ovariectomized ewes, oestrogen administration increases the levels of E z and P receptors in endometrial and whole uterine cytosol preparations, whereas the administration of P for several days to Ez-treated ewes diminishes the cytosol levels of both receptors (Koligian and Stormshak 1977a;Stone et al , 1979Miller et al 1979). Similarly, the levels of both E z and P receptors decline during the luteal phase of the oestrous cycle when serum P levels are high (Koligian and Stormshak 1977b;Miller et al 1977).…”

Oestrogen receptors and protein synthesis in caruncular and intercaruncular endometrium of sheep before implantation

“…Neither the trophoblast (Gadsby et al, 1980) nor the endometrium (Findlay et (Koligian & Stormshak, 1977b;Stone et al, 1979;Miller et al, 1979). Whilst progesterone can decrease oestrogen receptors, it is without effect on oestradiol-induced protein synthesis, RNA : DNA ratio and enzyme activities in endometrial tissue of ovariectomized ewes Miller et al, 1979;Findlay et al, 1981). This apparent discrepancy may reflect differences in the function of the two major cell types in the endometrium (McCormack & Glasser, 1980), stromal cells predominantly in caruncular endometrium and epithelial cells predominantly in intercaruncular endometrium (Huslig, Fogwell & Smith, 1979).…”

“…Although oestradiol-17 ß can mimic the effects of pregnancy on endometrial protein synthesis Miller et al, 1979;Findlay et al, 1981) and uterine blood flow (Huckabee, Crenshaw, Curet, Mann & Barron, 1970) there is no conclusive evidence that this steroid is involved. Neither the trophoblast (Gadsby et al, 1980) nor the endometrium (Findlay et (Koligian & Stormshak, 1977b;Stone et al, 1979;Miller et al, 1979). Whilst progesterone can decrease oestrogen receptors, it is without effect on oestradiol-induced protein synthesis, RNA : DNA ratio and enzyme activities in endometrial tissue of ovariectomized ewes Miller et al, 1979;Findlay et al, 1981).…”

“…That synthesis of protein in endometrium of non-pregnant ewes is under the control of ovarian steroids is now well established (Stone, Murphy & Miller, 1978;Stone et al, 1979;Miller et al, 1979;Findlay et al, 1981 (Greiss & Anderson, 1970;Greiss & Miller, 1971), suggesting that this is unlikely. Although oestradiol-17 ß can mimic the effects of pregnancy on endometrial protein synthesis Miller et al, 1979;Findlay et al, 1981) and uterine blood flow (Huckabee, Crenshaw, Curet, Mann & Barron, 1970) there is no conclusive evidence that this steroid is involved. Neither the trophoblast (Gadsby et al, 1980) nor the endometrium (Findlay et (Koligian & Stormshak, 1977b;Stone et al, 1979;Miller et al, 1979).…”

Differential hormonal regulation of estrogen receptors ERα and ERβ and androgen receptor expression in rat efferent ductules

“…However, it is necessary to highlight the fact that ER subtypes were not differentiated in that study, nor was the regulatory effect of estrogen and DHT investigated. In addition, other studies have shown differences in sex steroid receptor expression and steroid hormone action along the female reproductive tract between ruminants and other mammals (Miller et al 1979, Stone et al 1982, pointing to species differences in ER regulation. Differences in ER distribution in the male tract of rat and goat can be exemplified by the negative staining of goat efferent ductule ciliated cells and Leydig cells in the testis, both of them being positive for ERs in the rat.…”