Effect of various doses of catecholestrogens on uterine eosinophilia in the immature rat

This paper describes the induction of uterine eosinophilia as well as of deep endometrial edema and increase of uterine wet weight in the immature rat by the catecholestrogens 2-OH-estradiol and 4-OH-estradiol. These effects are thought to be mediated by eosinophils via a specific eosinophil receptor system. 4-OH-estradiol was equipotent with estradiol, whereas the effect of 2-OH-estradiol was significantly weaker.     

Effect of propranolol on various parameters of estrogen stimulation in the rat uterus

Summary Pretreatment with propranolol does not modify the estrogen-induced uterine eosinophilia, the water imbibition effect, nor the increase in uterine RNA and protein content. This confirms the independence of these parameters from the estrogen-induced early increase in uterine cAMP, since, when observed, the latter is suppressed by propranolol pretreatment.Acknowledgments. This work was supported by a contract of the Ministère de la Politique Scientifique, within the framework of the Association Euratom—University of Brussels—University of Pisa, and by grant 2015 from the Oficina Técnica de Desarrollo Científico y Creación Artística of the University of Chile.     

The involvement of the renin-angiotensin system in the regulation of cell proliferation in the rat endometrium

Oestrogens are known to enhance angiotensin biosynthesis by increasing the elaboration of its precursor, angiotensinogen. On the other hand, we found that inhibition of angiotensin-converting enzyme (ACE) suppressed the proliferative response of the rat anterior pituitary gland to oestrogens. To answer the question whether the angiotensin system is involved in the control of the cell proliferation of the uterine epithelium, the effects of an ACE inhibitor, enalapril maleate, and of angiotensins II and IV, alone or together with losartan, an antagonist of angiotensin receptor type 1 (AT1), on endometrial epithelial cell proliferation have been studied. The experiments were performed on ovariectomized female Wistar rats. In the first experiment the animals were injected with a single dose of oestradiol benzoate or received an injection of solvent only. Half of the oestrogen-treated rats were injected additionally with enalapril maleate (EN, twice daily). The incorporation of bromodeoxyuridine (BrDU) into endometrial cell nuclei was used as an index of cell proliferation. It was found that oestradiol alone dramatically increased the BrDU labelling index (LI) of endometrial cell nuclei, and this effect was partially blocked by the simultaneous treatment with EN. In the second experiment, the animals were injected intraperitoneally with angiotensin II (AII), angiotensin IV (AIV) or saline, alone or together with losartan. It was found that AIV induced an increase in the LI in uterine epithelium, and this effect was not blocked by the simultaneous treatment with losartan. The increase in LI in uterine epithelium was also observed in the rats treated with AII and with losartan. These findings suggest an involvement of angiotensin IV in the control of uterine epithelium cell proliferation. Received 12 October 1998; received after revision 6 January 1999; accepted 2 February 1999     

Colchicine-estrogen interactions

Summary Colchicine does not block estrogen-induced recognition of uterine blood vessel surface by eosinophils, but interfers with their migration through endothelial lining and therefore blocks estrogen-induced uterine eosinophilia and edema.Acknowledgments. This work was supported by grant 4002 from the Servicio de Desarrollo Científico y Creación Artística of the University of Chile. Technical help of Mr D. Sáez is appreciated.     

Effects of arsenite and oxamate on the in vitro functional activity of estrogen-dominated rat uterine horns

Summary Arsenite but not oxamate produce in vitro a distinct depression of estrogen-dominated uterine motility, both in the absence of substrate as well as in the presence of exogenous glucose or lactate. The addition of oxamate to preparations suspended in a medium with lactate as the sole external substrate ameliorates the depression of uterine motility elicited by arsenite.This work has been supported by grants 6638 and 6294 from the Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina.Senior Investigator of the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina.Junior Investigator of the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina.     

Constituents ofCannabis sativa L. XXI: Estrogenic activity of a non-cannabinoid constituent

Summary A non-cannabinoid phenol (4,4,dihydroxy-5-methoxybibenzyl) increased uterine weight in prepubescent female rats, suggesting non-cannabinoids contribute to the estrogenic effects ofCannabis.Acknowledgments. This research was supported by Contract 271-78-3527 from the National Institute on Drug Abuse and by the Research Institute of Pharmaceutical Sciences, University of Mississippi. The authors are grateful to Karen S. Tomaszewski for technical assistance.     

Effect of theophylline and triiodothyronine on some early estrogenic responses in the rat uterus

Summary Theophylline increases and triodothyronine decreases uterine edema induced by physiological doses of estradiol-17. Both of them decrease estrogen-induced uterine eosinophilia and the number of blood eosinophils, suggesting an explanation for the results in the uterus.Acknowledgments.—We wish to thank Dr G. Pineda, Salvador Hospital, Santiago, for the gift of L-triiodothyronine (Sigma). This work was supported by grant B 012-783, Servicio de Desarrollo Científico y Creación Artística, University of Chile.     

A study of granulated metrial gland cell differentiation in pregnant,macrophage-deficient,osteopetrotic (op/op) mice

A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant,op/op mice were studied histologically. GMG cell differentiation appeared to progress normally inop/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient inop/op mice.     

Biological activities of pure prostaglandins

Prostaglandins, the hydroxy unsaturated C20 fatty acids, are found throughout the body and have an equally wide range of biological activities. Prostaglandins are known to: 1) stimulate uterine contraction; 2) inhibit spontaneous contraction of the rabbit uterus; 3) inhibit the respiratory smooth muscle of different animals; 4) lower systemic arterial blood pressure when injected intravenously; 5) stimulate contractions in isolateral segments of intestinal smooth muscle of most species investigated; 6) produce transient sedation when intravenously injected in cats, and 7) inhibit lipolysis induced by catechal amines, corticotrophin, glucagon and thyroid stimulating hormone. The inhibitory and excitatory effects of prostaglandins may each have a physiological importance at different sites. Current state of knowledge of the distribution, metabolism and actions of the prostaglandins is still fragmentary. The functional significance of the prostaglandins is yet to be determined.     

Effect of Progesterone on the in vivo binding of estrogens by uterine cells

Summary Progesterone selectively inhibits estradiol upltake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.Acknowledgments. This work was supported by Grant No. 2015 From the Oficina Técnica de Desarrollo Cientifico y Creación Artística of the University of Chile.     

Uterine secretion during the sexual cycle in the rat and its capacity to disperse corona cells in vitro

Summary It was found that closure of the uterus disturbed the first 2 cycles after the operation; there-after the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion.     

[2-o-Iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin: Basic pharmacology and comments on their potential use in binding studies

Summary Both [2-o-iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin display only weak vasopressor and antidiuretic effects on rats. They inhibit the in vitro uterotonic action of oxytocin; this inhibition is not fully competitive. It is concluded that they are not suitable as markers for studies of uterine receptor for oxytocin.Supported by the Swiss National Science Foundation, grant No. 3.2080.73.Deceased 30 April 1975.     

Uterine secretion during the sexual cycle in the rat and its capacity to disperse corona cells in vitro.

It was found that closure of the uterus disturbed the first 2 cycles after the operation; thereafter the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion.     

Dissociation of separate mechanisms of estrogen action by actinomycin D

Summary Pretreatment with actinomycin D 1 h before estrogen administration completely blocks estrogen-induced increases in uterine RNA and protein content, but does not counteract estrogen-induced uterine eosinophilia, edema and increase in glycogen content.Acknowledgments. This work was supported by the Belgian Ministry of Scientific Policy (Concerted Actions of Research) and by the Servicio de Desarrollo Cientifico, Artistico y de Cooperacion Internacional from the University of Chile.     

Evidence that the establishment of pregnancy requires activation of lipoxygenase and phospholipase-A2

Summary The present work investigates the possibility that lipoxygenase products are involved in the biochemical mechanisms of blastocyst implantation by utilizing nordihydroguaiaretic acid (NDGA) and caffeic acid (CA), inhibitors of lipoxygenase enzymes, and quinacrine (QU), an inhibitor of phospholipase-A₂. It has been shown previously that inhibition of cyclooxygenase results in blockade of implantation. The inhibitors were dissolved in a standard medium and 5 l of the solutions were micro-injected into the uterine horns of day-4 pregnant mice. The contralateral horns acted as controls and received only vehicle. A sham-operated group provided normal controls. In 14 NDGA-treated mice, the control horns contained 40 implantations while the treated horns contained only 6 small implantations and 8 resorbing sites. These control horns were comparable to the sham controls. In 14 CA-treated mice, treated horns contained 17 small implantations plus 4 resorptions, whereas the control horns contained 26 small implantations and 4 resorptions. Twelve QU-treated mice exhibited 7 small implantations and 4 resorptions in the treated horns, plus 24 small sites and no resorptions in the control horns. Fourteen sham-operated mice had 95 implantation sites and no resorptions in their 28 horns. The results provide evidence for the involvement of the lipoxygenase enzymes and phospholipase-A₂ in the initial implantation process and in the subsequent development of early pregnancy.     

Activité gonadotrope d'un extrait d'urines de femmes en ménopause

Summary In agreement with earlier observations on hypophysectomized male rats, a purified extract from pooled menopausal urine has been shown to contain follicle-stimulating (FSH) as well as luteinizing (LH) activity. Its administration to immature hypophysectomized female rats increased ovarian and uterine weights and induced follicle growth and the formation of corpora lutea. If the activity of the extract is measured in standardized units by bioassay in intact female mice using the uterine weight, the dose needed for corpus luteum formation in the hypophysectomized female rat seems to be approximately ten times higher than the dose producing interstitial cell repair and complete spermatogenesis in the hypophysectomized male.

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2^e Communication: Effets sur les ovaires de rates impubères hypophysectomisées.     

Effects of multiple injections of luteinizing hormone-releasing hormone in the induction of pregnancy in androgenized female rats

Summary A study of the effect of cyclic (every 4 days) administration of gonadotropin releasing hormone on reproductive performance of the androgenized female rat was carried out. The responses measured were indirect indices of increased gonadotropin output; ovulation rate, uterine decidualization, mating and implantation.     

Endotoxin-induced acceleration of ovum transport in rabbits

Summary Salmonella enteritidis-Boivin endotoxin (1–20 g/kg) induced accelerated oviductal ovum transport in rabbits in a dose-related manner. Indomethacin prevented this effect. Levels of prostaglandin E and F in uterine vein blood increased following endotoxin injection.Deceased 6 December, 1977.Thanks are due to Elizabeth Menchaca, Larry Coons and Lenore Weinberg for technical assistance, and to Merck, Sharp, and Dohme for the gift of indomethacin. This work was supported by Rockefeller Foundation, NIH (HD-09339) and WHO (S76119). G. V. is a Rockefeller Foundation Postdoctoral Fellow in Reproductive Biology. Reprint requests to M. J. K. Harper.     

Effects of multiple injections of luteinizing hormone-releasing hormone on the induction of pregnancy in androgenized female rats

A study of the effect of cyclic (every 4 days) administration of gonadotropin releasing hormone on reproductive performance of the androgenized female rat was carried out. The responses measured were indirect indices of increased gonadotropin output; ovulation rate, uterine decidualization, mating and implantation.     

Effects of female sex hormones on polyamine-oxidizing enzyme activities and polyamine concentrations in immature rat uterus and liver

17-estradiol (E₂) and progesterone (P) treatment of immature female rats (10 g/100 g body weight) respectively resulted in 1.38-fold (p<0.02) and 1.42-fold (p<0.02) increase in the uterine polyamine oxidase activity, and 2.45-fold (p<0.001) and 1.43-fold (p<0.02) increase in the uterine diamine oxidase activity, as compared to the controls. E₂ caused a 5-fold (p<0.05) and a 1.36-fold (p<0.05) increase in putrescine and spermidine concentration respectively in rat uterus. Increases of 1.7-fold (p<0.02) and 1.6-fold (p<0.05) in putrescine and spermine concentration were determined in the P-treated uterus, as compared to the controls. The spermidine/spermine ratio, which is regarded as an index of growth rate, was higher in the E₂-treated uterus and lower in the P-treated uterus than in the control uterus. No statistically significant hormonal effects were estimated in the immature liver. The data reported suggest the possibility of an involvement of polyamine-oxidizing enzymes in the modulation of polyamine concentrations in rat uterus by the female sex hormones.