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Search for other papers by AUDREY E. LEE in
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SUMMARY
Continuous oestrogen stimulation produced an initial increase in mitosis and [3H]thymidine incorporation in the mouse uterine luminal epithelium on days 2 and 3 of treatment, but activity fell to the level of the untreated uterus on days 4 and 5. The implications of this control of cell division are discussed. A second wave of activity occurred about a week later, and in the longest experiment a third wave was seen on days 19 to 21. This pattern was similar to that seen in the glandular epithelium. There was little cell division in the stroma or myometrium. The rhythm was not due to diurnal variation. It was seen after treatment with oestrone and oestradiol, given either by injection or in the drinking water.
Search for other papers by M. P. BROGI in
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SUMMARY
The ability of regenerating cortical tissue, under the stimulus of sham adrenalectomy, to prevent the increase in the water content of the uterus caused by oestrogen has been followed at various intervals after adrenal enucleation.
A normal adrenal response was still absent 35 days after the operation but was re-established after 48 days. The significance of these findings is discussed.
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Search for other papers by Y. KOCH in
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Search for other papers by S. A. LAMPRECHT in
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Search for other papers by H. R. LINDNER in
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SUMMARY
The hypothesis that cyclic AMP plays an essential role in mediating the biological action of oestradiol on the uterus, was tested by determining the tissue concentration of the cyclic nucleotide after incubation of uteri of immature rats with oestradiol or after injection of this steroid into immature or ovariectomized rats. The effect of known stimulants of uterine adenyl cyclase, namely β-adrenergic drugs and prostaglandin E2 (PGE2), on the level of cyclic AMP in the uterus was also examined both in vitro and in vivo.
In either system, oestradiol failed to enhance the concentration of cyclic AMP in the uterine tissue, whereas adrenaline or the almost purely β-adrenergic agonist isoprenaline (isoproterenol) caused cyclic AMP accumulation that was susceptible to inhibition by the β-adrenergic blocking agent propranolol. Prostaglandin E2, and to a much lesser degree prostaglandin F2α, increased cyclic AMP concentration in the uterus, but the effect of PGE2 was not inhibited by propranolol. It may be concluded that oestradiol does not cause appreciable stimulation of PGE2 synthesis or activation of β-adrenergic receptors in the rat uterus since, otherwise, increased cyclic AMP production should have been observed after the treatment with oestradiol.
Isoprenaline mimicked the stimulatory action of oestradiol on uterine ornithine decarboxylase. However, this action of isoprenaline was abolished by propranolol, whereas that of oestradiol was only slightly, though significantly, inhibited.
The present findings do not support the view that the action of oestradiol on the uterus is mediated by cyclic AMP, and also suggest that β-adrenergic receptors and PGE2 can have only a minor role, if any, in the mechanism of action of this hormone.
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Search for other papers by A. W. ROGERS in
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SUMMARY
The distribution of radioactivity was studied autoradiographically in the uterus of the ovariectomized rat from 1 to 7 h after the s.c. injection of [3H]progesterone. Luminal and glandular epithelia were less radioactive than stroma or muscle. Grain densities over nuclei were the same as those over cytoplasm in the epithelial tissues and the muscle. Pretreatment with non-radioactive progesterone did not alter the pattern of distribution of radioactivity though in one experiment grain densities were significantly decreased in the pretreated animal; this decrease involved nucleus and cytoplasm in epithelial cells and in the muscle.
The interpretation of grain densities after the administration of [3H]progesterone is complicated by the presence of labelled metabolites. Further experiments were therefore carried out with [3H]megestrol acetate, a progestin which is not significantly metabolized in the uterus or plasma during the first 3 h after injection s.c. At 30 min, 1 and 2 h after [3H]megestrol acetate administration, the stroma and muscle were twice as radioactive as the epithelial tissues of the uterus. Nuclear and cytoplasmic grain densities were the same, both in the luminal epithelium and the stroma. Pretreatment with non-radioactive progesterone decreased the observed grain densities by 20–30% in all tissues including the extracellular spaces of the stroma. Though stromal cells were more radioactive than the surrounding extracellular spaces 1 h after [3H]megestrol acetate, the luminal epithelium was significantly less radioactive.
These results are consistent with the hypothesis that binding sites for progesterone are at relatively low concentrations in the uterus of the ovariectomized rat, that they are widely distributed in the uterus, and that after binding to these sites progestins are distributed between nucleus and cytoplasm in approximately equal proportions.
Search for other papers by R. N. MURDOCH in
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Search for other papers by I. G. WHITE in
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SUMMARY
The activity of several enzymes has been measured in the uterine endometrium of the rabbit during oestrus and pseudopregnancy and after injecting oestradiol benzoate or progesterone 28 days after ovariectomy. The enzyme activity of the uterine fluid has been determined during oestrus and the effect of uterine ligation studied.
Progesterone and the induction of pseudopregnancy stimulated succinic dehydrogenase (SDH) and glucose-6-phosphate dehydrogenase (GDH) activity and depressed amylase and lactic dehydrogenase (LDH) activity. In ovariectomized does, glutamate-oxaloacetate transaminase (GOT) activity increased after the injection of progesterone. Progesterone also stimulated endometrial phosphatase after ovariectomy but, when given after a period of oestrogen treatment, it limited the even greater response of acid and alkaline phosphatase to oestrogen; the activity then attaining the same level as when progesterone alone was given.
SDH, GDH and glycerylphosphorylcholine (GPC) diesterase could not be detected in uterine fluid but amylase and alkaline phosphatase were in greater concentration than in the endometrium. GPC diesterase was, however, found to be present in uterine tissue. Ligation of the uterus did not significantly alter the enzyme activity of the endometrium.
Search for other papers by MC Erlandsson in
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Search for other papers by CA Jonsson in
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Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.
Search for other papers by PE Milhiet in
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Heparin affin regulatory peptide (HARP), also named pleiotropin, is a secreted polypeptide that belongs to a new family of heparin-binding growth/differentiation factors. In this study, we investigated the expression and distribution of HARP mRNA and protein in rat uterus. Semi-quantitative reverse transcriptase PCR experiments showed variations in HARP mRNA levels throughout the estrous cycle, with a maximum during diestrus, pointing to hormonal regulation of HARP mRNA expression. Uterine expression of HARP mRNA was studied in ovariectomized animals treated with 17 beta-estradiol, progesterone alone or progesterone and RU486. In these experiments, progesterone upregulated HARP mRNA expression. Induction was observed 6 h after progesterone injection and was inhibited by RU486 treatment. In contrast, after 17 beta-estradiol injection, a slight decrease in HARP mRNA expression was observed. In situ hybridization studies with digoxigenin-labeled DNA probe revealed that HARP mRNA was present in smooth muscle cells of both myometrium and blood vessels and also in endothelial cells from endometrium. Immunohistochemical studies showed that HARP expression was not limited to cells that expressed HARP mRNA, but also occurred in both the luminal and glandular epithelium even though its transcript was never detected. We conclude that HARP may mediate the effects of progesterone on the homeostasis and vascularization of uterine tissue.
Search for other papers by M. M. JOSEPH in
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Biology Department, University of Zambia, P.O. Box 2379, Lusaka, Zambia
(Received 18 July 1975)
Traumatization makes the uterus of ovariectomized rats sensitive to exogenous prolactin (Joseph & Mubako, 1975). The presence of intra-uterine devices induces uterine hypertrophy and concurrently increases the production of prostaglandin F (Lau, Saksena & Chang, 1974; Saksena & Harper, 1974). In another recent report prolactin has been shown to stimulate the synthesis of prostaglandin-like material in the rat mesentery (Horrobin, Manku, Karmazi, Nassar & Greaves, 1974). Pharris & Hunter (1971) have demonstrated that prostaglandin F2α could enhance the uterine growth promoting effect of pregnant mare serum gonadotrophin in the immature rat. All this evidence led Joseph & Mubako (1975) to conclude that prostaglandins might be involved in the extra-ovarian stimulatory effect of prolactin on the traumatized uterus in the rat. The study reported here was carried out to determine whether prostaglandin F2α could imitate, or synergise
Search for other papers by J. F. WOESSNER Jr in
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Departments of Biochemistry and Medicine, University of Miami School of Medicine, P.O. Box 520875, Biscayne Annex, Miami, Florida 33152, U.S.A.
(Received 24 February 1976)
Ovarian secretion of oestradiol falls from 0·7 μg/day to undetectable levels shortly after parturition in the rat (Yoshinaga, Hawkins & Stocker, 1969). Administration of oestradiol during the post-partum period retards involution of the uterus and breakdown of collagen (Woessner, 1969). A significant inhibition of collagen degradation is produced by a dose of 1 μg oestradiol/day administered i.p. to parturient rats, and maximum effects are produced by 100 μg/day (Woessner, 1969). Oestradiol acts, directly or indirectly, to reduce the assayable level of collagenase in the uterus (Ryan & Woessner, 1974). The high doses of oestradiol necessary to produce these effects raise the possibility that the effects are non-specific or that there may be metabolism of oestradiol to other products that are the active compounds. This possibility has
Search for other papers by G. M. STONE in
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SUMMARY
17α-Ethyl-19-nortestosterone and MER-25 inhibited the early uptake of oestradiol by the uterus and vagina when both inhibitor and oestrogen were administered subcutaneously. The oestrogen-induced growth in the uterus and vagina was also inhibited by both compounds. Inhibition with 17α-ethyl-19-nortestosterone was greatest when it was injected at the same time as the oestradiol. It was not possible to obtain any inhibition of the oestrogenic response by systemic administration of dimethylstilboestrol although it seems that its oestrogenic metabolites will compete with the natural oestrogen for receptors in the target organ.
With intravaginal injection MER-25 inhibited the rapid uptake of oestradiol while 17α-ethyl-19-nortestosterone had no effect. However, the activity retained in the vagina 20–180 min. after the injection of oestradiol was decreased by 17α-ethyl-19-nortestosterone.
