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Biology Unit, Institute of Interdisciplinary Research, Free University of Brussels, 115 B Waterloo, 1000-Brussels, Belgium and *Service de Médecine et Laboratoire d'Investigation Clinique, Institut J. Bordet, 1000-Brussels, Belgium
(Received 19 April 1977)
We wish to report evidence for the early induction by oestradiol-17β of a protein in mammary tumours induced in Sprague–Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA). The protein appears to be analogous to the oestrogen-induced protein first discovered in the rat uterus by Notides & Gorski (1966) and widely known as 'induced protein' (IP). Induction of IP by oestradiol-17β has been demonstrated in rodents in several tissues of the female genital tract that are targets for oestrogens (Katzman, Larson & Podratz, 1971; Katzenellenbogen & Leake, 1974; Dupont-Mairesse & Galand, 1975) and correlated with the rate of nuclear accumulation of oestrogen receptors (Katzenellenbogen & Gorski, 1972; Katzenellenbogen, 1975). Therefore, the search for induction of IP in DMBA-induced mammary tumours containing oestrogen
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SUMMARY
In this study of lipid metabolism of the rat uterus during early pregnancy, lipids were extracted after incubation with [1,2-14C]acetate or after its administration in vivo. The results indicated that the synthesis and concentration of triglyceride increased with time after mating. Triglyceride accumulated in uterine tissue before implantation and was depleted in tissue from implantation areas by day 7. Synthesis of fatty acid increased with time after mating, as did the concentration of various lipids other than cholesterol in the free sterol fraction. Supporting the concept that lipids are necessary during early embryonic development, the results suggest that the rat utilizes endometrial fatty acid esterified to triglyceride. No trends related to time were seen in the rate of synthesis nor in the concentration of sterol ester or free fatty acid; hence, specific concentrations of these lipids are probably not necessary for embryonic development during early pregnancy.
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SUMMARY
In the normal non-pregnant guinea-pig uterus, proliferation of the surface epithelium occurred principally on day 3 after oestrus (vaginal opening). Intense mitotic activity occurred on the following day in the lower regions of the glands. Mitotic activity was pronounced in the endometrial stroma on the succeeding 2 days.
In the ovariectomized guinea-pig, oestrogen stimulated cell devision only in the surface and superficial glandular epithelia, but conditioned the endometrium to respond to progesterone so that at least 2 successive days of progesterone treatment after oestrogen priming elicited both intense glandular proliferation and extensive stromal cell division, while progesterone alone induced uterine closure.
The proliferative responses of the guinea-pig endometrium thus resembled the responses of the rabbit endometrium rather than the rat or mouse endometrial reaction to hormonal stimulation.
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SUMMARY
The effect of doses of oestradiol ranging from 0·0125 to 1·6 μg on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0·32 μg. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0·0125–0·2 μg) was significantly increased.
When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0·0125 μg oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0·05 μg oestradiol was administered, histamine did not modify the increase already produced by the hormone.
Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake.
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The deciduogenic action of various kinds of prostaglandin (PG), i.e. PGE1, PGE2, PGF2α and PGI2, methylated prostaglandins (15-met-PGE1, 15-met-PGE2 and 15-met-PGF2α), PGF2α-13-dehydro analogues (13-DH-PGF2α, ent-15-epi-13-DH-PGF2α), endoperoxide analogues (15S)-hydroxy-9α,11α-(epoxymethano)-prosta-5Z,13E-dienoic acid (U 44069) and (15S)-hydroxy-11α,9α-(epoxymethano)-prosta-5Z,13E-dienoic acid (U 46619), and of the prostaglandin precursor, arachidonic acid, has been demonstrated after intraluminal instillation of these compounds into the uterus of immature rats sensitized with progesterone alone. Under this minimal hormonal stimulation, in which a trauma (a scratch) of the endometrium is required to induce the decidual response, all these compounds elicited the formation of deciduomata, substantiating the suggestion that the scratch-induced decidual reaction is mediated through release of prostaglandin. Confirmation was obtained through the effect of indomethacin and cortisol, both of which decreased the decidual response brought on by a scratch or by arachidonic acid, whereas the effect of PGF2α was decreased by indomethacin but not by cortisol. Histamine, thromboxane B2, and oleic, palmitic and homo-γ-linolenic acids were not deciduogenic.
A dose-dependent inhibitory effect of indomethacin on deciduoma formation by instillation of oil into animals sensitized by progesterone plus oestradiol was also observed.
The results support the proposal that the decidual reaction involves prostaglandins and we suggest that the deciduoma is a valuable model for studying the action of prostaglandin-related compounds.
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SUMMARY
In the uterus of pregnant mice an increase in uptake of tritiated uridine occurs between days 2 and 3 of pregnancy, followed by a further increase from day 4 onwards. Uridine uptake changes in the same manner in pseudopregnant mice up to day 4, but thereafter declines to a minimum at day 6. The non-pregnant horn of the unilaterally pregnant mouse shows the same changes as the uterus of the pseudopregnant mouse. The results suggest that implantation occurs during a period of declining ovarian stimulation of the uterus and that the increased uptake of uridine in pregnant mice is stimulated locally by implantation.
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Progesterone and megestrol acetate reduced oestrone-stimulated epithelial mitosis in the mouse uterus and increased it in the stroma. Neither progestin reduced the uptake of [3H]oestradiol by the uterus in vivo. Compounds ICI 46,474 and U11,100A were mitogenic in both luminal epithelium and stroma but did not antagonize the epithelial response to oestrone. U11,100A reduced the uptake of [3H]oestradiol by the uterus in a way similar to that shown by unlabelled oestradiol, but there was no evidence that ICI 46,474 competed for oestrogen receptors.
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SUMMARY
The uterus, ovary and kidney of rats treated with fluoroacetate accumulated large quantities of citrate. It was inferred that a citric acid cycle operates in the uterus, ovary and kidney of castrated and normal rats. After the administration of oestrogen, citrate accumulation 3 hr. after fluoroacetate was slightly increased at 24 hr., but much reduced 96 hr. after the oestrogen had been injected.
It is postulated that during the first 24 hr. after oestrogen injection, oxidative respiration by way of the citric acid cycle takes place. Thereafter alternative metabolic pathways may predominate, the citric acid cycle in the uterus being depressed.
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The uterus masculinus of the adult rabbit is a large bilobed sac lying behind the bladder; it opens into the prostatic portion of the urethra and is lined by a complex epithelium [Plate I, Fig. 1]. The degree of complexity varies in different breeds of rabbits, and of those studied the Himalayan shows the most highly developed epithelium. In this breed, complexity of the epithelium is comparable to that seen in the progestational rabbit uterus, though it is clearly different in nature and development. Hütt [1927], who discusses the earlier literature, gives an excellent description of the uterus masculinus. Some doubt exists as to its embryological origin in the rabbit. Kölliker [1879] and other nineteenth-century embryologists found that the Müllerian ducts tended to atrophy in the foetus, although traces of them might occasionally persist. Hütt concludes that it is on the whole unlikely that the uterus masculinus is of Müllerian
