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Progesterone in the uterus. V. Correlation of the in vitro progesterone metabolism with the progesterone binding in rat uterus.

Incubations of rat uterine segments with varying 3H-progesterone concentrations were performed to study the hormone uptake by the tissue. The radioactivity of the uterus and the nutrient medium were plotted in form of a SCATCHARD plot. Additionally, the binding capacity of the uterine cytosol was measured. In both systems, the hormone was found to be associated with two components which differ from each other in their association constants. The progesterone metabolism occuring at a hormone concentration of 10(-6)M and more in the incubation medium is discussed with respect to the affinity and the capacity of the hormone binding components.

Animals

Progesterone in the uterus. X. Dependence of the in vitro progesterone metabolism on progesterone binding in rat uterus.

The effect of estrogen pretreatment was stud-ed on the in vitro metabolism and binding of progesterone in uteri of ovariectomized rats in order to prove the dependence of the metabolism of progesterone on its binding. For this purpose, the extent of progesterone binding was varied in uterine tissue by different estrogen treatment of the rats and compared with the metabolism under the same conditions. The protein content determined in 100 mg tissue was used as parameter indicating the success of the pretreatment. Estrogen exposure of the rats for 30 or 45 hrs. caused a rise of protein amount in uterine tissue which was accompanied by an increase of binding sites of progesterone binding components. The binding sites were determined by charcoal adsorption technique and SCATCHARD-analysis. Under nearly the same success of estrogen pretreatment, the increase of the portein amount and with it the rise of binding sites reduced the amount of progesterone metabolites in uterine tissue. The metabolites were determined by quantitative TLC-analysis of the recovered compounds from uterine segments after incubation with radioactive progesterone. Additionally, an enlarged metabolic rate could be observed after saturation of binding components. It is concluded from the results of these experiments that progesterone binding components are factors limiting the enzymatic conversion of progesterone in rat uterus.

Animals

The temperature, pH, and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle.

Changes in the temperature, pH, and partial pressure of oxygen (PO2) in the cervical canal and cavum uteri were measured in women with or without an intrauterine device and in the uteri of rats throughout the cycle. Only the PO2 exhibited significant variations, rising during the ovulatory phase in both cervices of women and uteri in rats. It is speculated that the rise in PO2 is related to the function of these organs as reservoirs for spermatozoa.

Adult

[Carcinoma of the uterus in the Austrian mortality statistics. 1. Carcinoma of the uterus in Viennese autopsy reports 1976 (author's transl)].

The official mortality statistics in Austria fail to report the localization of uterine cancer in nearly two thirds of cases and, thus, the annual death rate of women with cervical versus endometrial cancer is not clear. These two diseases behave totally differently with regard to their aetiology, age distribution, early diagnosis, therapy and prognosis and, therefore, a separate analysis is necessary. This study presents an analysis of the incidence of uterine cancer in a series of 7,276 women who died in Vienna hospitals in 1976. Of the 151 cases (2% of all the women in the examined collective) 106 died of cervical carcinoma, 33 of endometrial carcinoma and 9 of unspecified uterine carcinoma. The average age of women who died of cervical carcinomas was 60 years, whilst that of patients with endometrial carcinoma was 71.7 years. In 12.6% of cases double carcinomata were found. The relation between deaths from cervical carcinoma to endometrial carcinoma is 3.3:1. If this ratio is applied to the 942 deaths from uterine carcinoma in 1976 in Austria, then one can estimate that more than 700 women must have died of cervical carcinoma and more than 200 of endometrial carcinoma. The 303 deaths from cervical carcinoma and 65 from endometrial carcinoma reported in the official mortality statistics are, therefore, totally misleading and ought not to be used as a basis for epidemiological investigations.

Austria

[Carcinoma of the uterus in the Austrian mortality statistics. I. Carcinoma of the uterus in Viennese autopsy reports 1976 (author's transl)].

The official mortality statistics in Austria fail to report the localization of uterine cancer in nearly two thirds of cases and, thus, the annual death rate of women with cervical versus endometrial cancer is not clear. These two diseases behave totally differently with regard to their aetiology, age distribution, early diagnosis, therapy and prognosis and, therefore, a separate analysis is necessary. This study presents an analysis of the incidence of uterine cancer in a series of 7,276 women who died in Vienna hospitals in 1976. Of the 151 cases (2% of all the women in the examined collective) 109 died of cervical carcinoma, 33 of endometrial carcinoma and 9 of unspecified uterine carcinoma. The average age of women who died of cervical carcinomas was 60 years, whilst that of patients with endometrial carcinoma was 71.7 years. In 12.6% of cases double carcinomata were found. The relation between deaths from cervical carcinoma to endometrial carcinoma is 3.3:1. If this ratio is applied to the 942 deaths from uterine carcinoma in 1976 in Austria, then one can estimate that more than 700 women must have died of cervical carcinoma and more than 200 of endometrial carcinoma. The 303 deaths from cervical carcinoma and 65 from endometrial carcinoma reported in the official mortality statistics are, therefore, totally misleading and ought not to be used as a basis for epidemiological investigations.

Austria

Intracellular relationships of the oestrogen receptor in the rat uterus and hypothalamus during the oestrous cycle.

Simultaneous measurements were made of the specific oestrogen receptor in the nuclear and cytosol fractions prepared from the uterus and hypothalamus of 50--81-day-old female rats undergoing a 4-day oestrous cycle. In the uterus, the content of nuclear receptor fluctuated in concert with known cyclic changes in the secretion of oestrogen, being maximal at pro-oestrus. Over the period of 50--81 days, the nuclear content at all phases increased with age, again corresponding to known age-related increases in ovarian secretion of oestrogen. This age-related increase in nuclear content, averaged from the values of the different phases in each age group, was related to equivalent increases in uterine wet weight, an increase of 1 pmol of receptor being accompanied by an increase of 80--90 mg. The concentration of cytosol receptor was maintained constant, with respect to wet weight, throughout the cycle and with age, irrespective of changes in nuclear content. In the uterus of normal mature females, translocation of receptor into the nucleus did not lead to depletion of cytosol receptor, suggesting a process of continuous replenishment/synthesis. In the hypothalamus, the nuclear content of oestrogen receptor was also maximal at pro-oestrus. In contrast with the uterus, the content of hypothalamic cytosol receptor was minimal at this phase and reflects depletion of the cytosol receptor, possibly as a result of translocation. The extent of translocation was low compared with that in the uterus and did not alter with age during the age-period studied. This low nuclear binding of the receptor in vivo is discussed in relation to the presence of a cytosol factor, present in limiting amounts, which in vitro mediates the binding of cytosol receptor to oligo(dT)-cellulose. The difference in the physiological response of the uterus and of the hypothalamus to oestrogens may be related to the extent of nuclear binding of receptor.

Animals

New concepts on the action of oestrogens in the uterus and the role of the eosinophil receptor system.

Two receptor systems for oestrogens have been demonstrated in the uterus: the cytosol-nuclear receptor system and the eosinophil receptor system. It has been proposed that the cytosol-nuclear receptor system mediates the genomic response to oestrogens in the uterus, while the eosinophil receptor system is thought to mediate the uterine edema and other early oestrogenic responses in the uterus. Cortisol is known to decrease drastically the number of eosinophils in the blood and therefore to limit their availability for migration to the uterus. The present results show that cortisol also drastically reduces both the oestrogen-induced uterine eosinophilia and the uterine wet weight responses, but does not interfere with the oestrogen-induced uterine RNA and protein increases. Oestradiol-17 beta has a higher affinity than oestriol for the cytosol-nuclear receptors and is now found to be the more potent oestrogen in inducing the genomic activation in the uterus. Estriol has a higher affinity than oestradiol-17 beta for the eosinophil receptors, and therefore, oestriol is the stronger oestrogen in inducing those oestrogenic effects which are mediated by the eosinophil receptor system. We conclude that the eosinophil receptor system for oestrogens is a new system, independent of Jensen's cytosol-nuclear receptor system, and this eosinophil receptor system is involved in the mechanism of oestrogen action in the uterus.

Animals

Influence of hCG injection and steroid treatment on prostaglandin metabolism by rabbit uterus and oviduct.

Metabolism of PGE-2 and PGF-2 alpha by cytosolic fractions (100 000 g supernatant) of rabbit uterus, oviduct and lung was measured in vitro. Metabolism of PGE-2 was greater than that of PGF-2 alpha for oviduct and uterus. After an ovulating injection of hCG metabolism of both PGE-2 and PGF-2 alpha by lung and uterus declined linearly up to 72 h (during the time of ovum transport). The amount of PG metabolism by the oviduct did not change significantly during this period, but the percentage changes of PGE-2 and PGF-2 alpha metabolism from oestrous values did differ, and perhaps indicated a change in the ratio of intracellular PGs. No change of metabolism of either PG by lung, uterus or oviduct occurred at 24 or 72 h after an injection of 250 micrograms oestradiol cyclopentylpropionate given concomitantly with the hCG (a treatment regimen which causes 'tube-locking' of ova). However, progesterone treatment, in a regimen known to cause accelerated transport of ova through the oviduct, caused significantly enhanced metabolism of both PGE-2 and PGF-2 alpha by uterus and oviduct, but not lung, 30 and 48 h later except for PGE-2 by uterus at 30 h. These results suggest that changes in metabolism of PGE-2 and PGF-2 alpha by the oviduct may be involved in the mechanisms controlling ovum transport.

Animals

Characterization of oxytocin receptors in the uterus and mammary gland.

High affinity binding sites for 3[H] oxytocin have been demonstrated in particulate fractions from rat uterus and oviduct, myometrium from the sow, ewe and human, ewe endometrium, and mammary gland from the lactating rat. The binding activity has been localized to enriched plasma membrane fractions from the rat uterus and mammary gland; cells isolated from the mammary gland also bind oxytocin. The apparent dissociation constant (Kd) for the interaction of oxytocin with its binding sites in a variety of tissue preparations is in the nanomolar range. The concentration of oxytocin eliciting half-maximal contraction of the rat isolated uterus corresponds to the apparent Kd of oxytocin interaction with uterine particulate fractions. Binding is specific with respect to the target tissue or cell, as well as to the ligand. The affinity of binding sites for oxytocin analogues corresponds generally to their potencies as agonists or antagonists. Factors that affect the binding of oxytocin affect the biological response in the same way. For example, certain divalent metal ions, which increase oxytocin binding activity, enhance the sensitivity of the contractile response of the uterus and mammary gland to oxytocin. Estrogen administration, which increases the uterine binding of oxytocin, increases the sensitivity of the myometrium to oxytocin. The myometrium binds the most oxytocin at estrus and is most sensitive to oxtocin at that time. The dgree of stimulation by oxytocin of prostaglandin F2alpha synthesis by ewe endometrium is paralleled by an increased concentration of oxytocin binding sites. The marked increase in sensitivity to oxytocin of the rat uterus occurring on the day of parturition also is reflected by the amount of oxytocin bound by the uterus. Because of the many correlations between oxytocin binding and bioactivity, it appears that oxytocin binding sites on the plasma membrane of target cells constitute the recognition part of oxytocin receptors.

Animals

[Arguments for a hesitamt attitude in the management of retroflexion of the pregnant uterus].

Among 5036 pregnant patients under prenatal care of a gynecologist, a retroflexion of the pregnant uterus was found in 438 cases (8.7%). The incidence of spontaneous abortion in the cases with retroflexion was 10.4%. This corresponds to the expected mean incidence of spontaneous abortion. In a control group of 1000 pregnancies without retroflexion of the uterus, the incidence of spontaneous abortion was 9.2%. The rate of premature delivery in cases with retroflexion was 5.3% and showed no difference to the control group without retroflexion (5.5%). Spontaneous anteflexion was awaited in all cases with retroflected pregnant uterus. Because of overflow incontinence manual anteflexion of the uterus at 15 weeks of gestation became necessary in one case. This pregnancy went to term. Because of our good results, we make a plea for expectant management of retroflexion of the pregnant uterus. Regular control examinations are necessary so that the lack of spontaneous anteflexion is not overlooked. Among 378 cases with a retroflected pregnant uterus which were followed to term, manual anteflexion became necessary in only one case.

Female

[Metric growth of the uterus in digenetic trematodes (author's transl)].

1. The length of the uterus of Dicrocoelium dendriticum, Pleurogenoides medians and Fasciola hepatica at different stages of development is correlated with the corrected size of the body (parallel length x breadth). 2. The data plotted in a log-scale show for all three species a sigmoid curve with linear middle section. 3. The function y = ax + ac(xw - x)3 + b(y = log length of the uterus, x = log length of the body, xw = log length of the body at the turning point) fits very well to the data obtained from Dicrocoelium dendriticum. The constants a, ac and b were determined numerically. The function is valid also for Pleurogenoides medians and Fasciola hepatica but with other constants. 4. The linear middle section of the sigmoid curve may be interpreted by allometric growth. During this phase of development the uterus is tubelike. 5. During the earliest stages of development the uterus forms a solid cord of cells (three-dimensional growth) and grows slower than in a later stage after formation of a cell-free interior (two-dimensional growth). 6. The latest phases of development are characterized by a small increase in length of the uterus due to the three-dimensional dilatation by the produced eggs. 7. The computed function is considered as a modification of the law of allometric growth Y = B . Xa, respectively y = ax + b (log Y = y, log X = x).

Animals

The action of bradykinin and oxytocin on the isolated whole uterus and myometrium of the rat in oestrus.

1. A technique is described for obtaining a myometrial preparation devoid of endometrium, from the uterus of the rat in oestrus. 2. Acetylcholine and prostaglandin F2alpha (PGF2alpha) produced concentration-effect curves with the same maximal tensions and slope on the whole uterus and myometrial preparations. Concentration-effect curves to bradykinin and oxytocin on the myometrial preparation were altered, resulting in a shift to the right and a decreased maximum response compared with those produced by the whole uterus. 3. Indomethacin produced greater antagonism of the responses of the whole uterus to bradykinin and oxytocin than to acetylcholine and PGF2alpha, whereas responses of the myometrium to all four agonists were similarly depressed. 4. Responses of the myometrial preparation to a range of concentrations of bradykinin and oxytocin were significantly enhanced by prior sensitization of the myometrium to PGF2alpha. This significant enhancing effect of PGF2alpha was only seen with the threshold dose of acetylcholine. 5. It appears that the mechanism of action of bradykinin and oxytocin on the rat uterus involves both a direct action and an indirect action. The indirect action possibly involves release of prostaglandin(s) from the endometrium.

Acetylcholine

Interactions of 17beta-estradiol and L-norepinephrine on the rat uterus.

Norepinephrine increased the in vitro uptake of 3H-estradiol by the uterus of spayed rats. This effect was observed at 15 and 30 min but not at 90 min. Norepinephrine also increased the binding of 3H-estradiol by the nuclear (p less than 0.02) and the cytosol fractions (p less than 0.01) when incubated with uterine homogenates, suggesting that norepinephrine does not require the presence of the intact tissue to exert its effects. The in vivo uptake of 3H-estradiol and the determination of the number of binding sites were performed in the uterus of rats treated with estradiol and estradiol plus norepinephrine. Norepinephrine alone increased the uptake of 3H-estradiol and the number of binding sites. The highest increment in both parameters was observed in the uterus of rats treated with estradiol plus norepinephrine. The estradiol Ka of the rat uterus cytosol treated with estradiol alone or plus norepinephrine was higher than that observed in the group without estradiol, suggesting the presence of different proteins that bind estradiol. These results indicate that norepinephrine increases the entrance of estradiol into the rat uterus both in vitro and in vivo.

Animals