PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Estrogens, Non-Steroidal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

Antiestrogens in treatment of breast cancer.

The antiestrogens represent a group of compounds, not necessarily steroidal, which are able to decrease the specific uptake of estrogens in vitro and in vivo by various target tissues in the rat and in man. This action is explained either by competitive binding to estrogen receptor sites or, more probably, by failure of the antiestrogen complex, translocated into the nucleus, to stimulate neoformation of receptors in the cytoplasm. This explains the transient estrogenic effect of antiestrogen. Antiestrogens used in humans are hormone specific and antagonize also non-steroidal estrogens, like stilbestrol. Three compounds have been used in advanced breast cancer with the same indications as the older hormonal treatments. They are clomiphene citrate, nafoxidine and tamoxifen. Nafoxidine and tamoxifen are probably equally active. The response rate is between 28 and 35%, with a median duration of nine months. Nafoxidine is toxic for the skin and tamoxifen is the preferred compound. A randomized trial comparing ethinyl estradiol and an antiestrogen showed similar rates of response with the two compounds in advanced breast cancer. The uniformity of results of treatment of advanced breast cancer by hormonal agents including antiestrogens and their limitations, probably justifies the present-day concept which assigns hormonal treatment a secondary role, either as a supplement to cytotoxic chemotherapy or for old and debilitated patients. However, as a supplemented to chemotherapy, hormonal agents are probably important since recent studies have shown that apparently all breast cancers have positive receptor sites, albeit in variable amounts. Because of their lack of toxicity, antiestrogens are probably the best hormonal agents available at present.

Adult↗
PubMed1979

Estrogen-induced efflux of endogenous catecholamines from the hypothalamus in vitro.

Short-term organ cultures of the intact hypothalamus were used to study the effects of various estrogenic compounds on catecholamine release. Estradiol-17 beta (0.1--20 microM) produced a concentration-dependent efflux of norepinephrine and dopamine while its biologically inactive enantiomer, estradiol-17 alpha, was ineffective at concentrations up to 20 microM. Diethylstilbestrol, a potent non-steroidal estrogen, was as effective as estradiol-17 beta in inducing catecholamine efflux. In contrast, weakly or non-estrogenic steroids such as estrone, estriol, and corticosterone were without effect. The time course of the estrogen-induced efflux of hypothalamic catecholamines was similar to that previously reported for the estrogen-induced accumulation of hypothalamic cAMP, providing further evidence for the involvement of catecholamines in this effect. Theses results suggest that estrogen may facilitate the release of catecholamines within the hypothalamus.

Animals↗
PubMed1977

Coagulative and fibrinolytic studies on postmenopausal women treated with a new non-steroidal oestrogen.

Treatment of postmenopausal women with a non-steroid oestrogen (P1496) in a dose of 50 mg a day for 2 ,days before operation for prolapse did not suppress the histochemically determined fibrinolytic activator content of the vessel wall. Neither was any change found in the concentration of P&P-complex (prothrombin, factor VII, factor X), factor VIII, antithrombin III, alpha1-antitrypsin, alpha2-macroglobulin or the inhibitors of urokinase induced plasminogen activation. Nothing suggested a thrombogenic effect of this non-steroidal oestrogenic compound.

Aged↗
PubMed1976

Cancer of the uterine corpus after hormonal treatment for breast cancer.

Among 45853 women in whom breast cancer was diagnosed after age forty-nine, from the series of the End Results Program of the National Cancer Institute, cancer of the uterine corpus subsequently developed in 203. The risk was greater among those women receiving hormones than in other treatment groups, and tended to rise with increasing interval from first treatment. One method of estimating an expected value indicated that the excess risk of corpus cancer in breast-cancer patients was restricted to those treated with hormones. Given the time period under study, it may be assumed that the hormones were primarily non-steroidal oestrogens.

Age Factors↗
PubMed1977

Carcinogenic and possible mutagenic effects of stilboestrol in offspring exposed in utero.

The relevant literature has been reviewed and it appears that there is no doubt that in utero exposure to stilboestrol is related to the eventual development of vaginal adenocarcinoma in young females. Although cancer of other types are also prevalent, the incidence is not great and may be related to other types of drugs taken during pregnancy. The review attempts to correlate the genetic effects with the abnormal development, but on account of the scarcity of data such correlation is not possible. Further work on the genetic effects and the development of the lower genital tract in the female needs to be carried out.

Abnormalities, Drug-Induced↗
PubMed1975

Flavonoids. 8. Synthesis and antifertility and estrogen receptor binding activities of coumarins and delta3-isoflavenes.

A series of coumarins and delta3-isoflavenes was prepared. Although antifertility activity was shown by all of these compounds, the required dosage in mice varied from 13.5 mug/kg/day to 50 mg/kg/day. The most potent compounds were the 2-methyl-4-ethylisoflavenes, two of which (2a and 2b) were about equipotent with DES on a molar basis. They were followed by the 2,2-dimethylisoflavenes, the 2-unsubstituted isoflavene, and the coumarins. The most active compounds possessed an acetoxy group at C-7 and an oxygen function at C-4'. Presence of fluorine at C-4' or diethylaminoethoxy at C-M decreased the antifertility activity. The uterotropic activity followed the same trends as the antifertility activity with some evidence for the separation of the two effects in the 2,2-dimethylisoflavene series. Based on a limited study it appears that two phenolic hydroxyl groups are required for the presence of good estrogen receptor binding activity. An apparent lack of correlation between the estrogen binding activity and uterotropic or antifertility effects is probably explained by in vivo metabolism.

Animals↗
PubMed1978

Toxicologic properties of fluorescent whitening agents.

From the collection of toxicologic data, it is seen that the fluorescent whitening agents are a well-investigated class of compounds. Only in one of the groups of compounds investigated did it appear advisable to discontinue the use of a particular product on the basis of the toxicologic findings. In the large number of the other cases, the findings indicate that there is a considerable degree of toxicologic safety in the use of the FWAs in soap and detergent products.

Animals↗
PubMed1979

The estrogenicity of delta-9-tetrahydrocannabinol (THC): THC neither blocks nor induces ovum implantation, nor does it effect uterine growth.

The estrogenicity of THC was assessed in three estrogen-sensitive systems. The drug did not block implantation when injected (s.c.) on Day 0 of pregnancy: on Day 6, 95% (3 mg/kg) and 86% (12 mg/kg) of the mice had embryos as did 96% (P greater than 0.1) of the controls; implantation occurred in only 9% (P less than 0.005) of mice treated similarly with estradiol (E2; 0.15 mg/kg). Nor did THC induce implantation: pregnant mice were ovariectomized on Day 1, treated daily with progesterone (2 mg, s.c.) and injected (i.p.) with THC on Day 3: at mg THC/kg 39% had embryos, as did 41% of those at 6 mg/kg; these rates do not differ (P greater than 0.99) from that of the controls (38%); in contrast, ova implanted in 75% (P less than 0.025) of E2-treated mice (4.0 microgram/kg). The average number of implanting ova was the same in all groups in both experiments. THC did not cause uterine hypertrophy: ovariectomized mice were injected (s.c.) for 14 days with THC (3 or 6 mg/kg) or E2(2 microgram/kg): the uterine weight, total uterine protein and total uterine glycogen of the ovariectomized controls was 24 +/- 2 mg, 3 +/- 0.3 mg and 11 +/- 3 mg respectively and the values for the THC-treated mice were not different (P greater than 0.05); in contrast, E2 increased (P less than 0.01) uterine weight to 139 +/- 9 mg, uterine protein to 5 +/- 0.6 mg and uterine glycogen to 62 +/- 8 mg. It is concluded that THC is not estrogenic.

Animals↗
PubMed1976

Alpha-fetoprotein: the major high-affinity estrogen binder in rat uterine cytosols.

Evidence is present that alpha-fetoprotein (AFP), a serum globulin, accounts mainly, if not entirely, for the high estrogen-binding properties of uterine cytosols from immature rats. By the use of specific immunoadsorbents to AFP and by competitive assays with unlabeled steroids and pure AFP, it has been demonstrated that in hypotonic cytosols AFP is present partly as free protein with a sedimentation coefficient of about 4-5 S and partly in association with some intracellular constituent(s) to form an 8S estrogen-binding entity. The AFP leads to 8S transformation results in a loss of antigenic reactivity to antibodies against AFP and a significant change in binding specificity. This change in binding specificity is manifested by an increase in binding affinity for estradiol, estriol, diethylstillbestrol, and nafoxidine ( a non-steroidal anti-estrogen), and by a concomitant decrease in estrone binding. Both the antigenic and binding properties of native AFP are recovered after dissociation of the 8S complex in 0.4 M KC1. An AFP-mediated mechanism of early intracellular events associated with estrogen entry in target cells is suggested and discussed with regard to current views on steroid action.

Animals↗
PubMed1975

Androgen-induced nuclear accumulation of the estrogen receptor.

The effect of androgens on the nuclear uptake of both tritiated estradiol (3H-E2) and the estrogen receptor was studied in immature rat uteri. It was demonstrated that in vitro preincubation of immature rat uteri with various androgens (1 muM to 50 muM) followed by incubation with 3H-E2 (20 nM) resulted in a greatly decreased specific nuclear uptake of 3H-E2. Non-androgenic steroids had no effect. It was also confirmed that 5alpha-dihydrotestosterone (DHT) causes the accumulation of the estrogen receptor in the nuclei of uterine tissue. In vitro incubations of rat uteri with DHT (1muM and 50muM) were found to cause maximal nuclear estrogen receptor accumulation to the same degree as caused by estradiol, i.e. the nuclear uptake of approximately 100% of the estrogen receptor. Antiandrogens, which block the binding of androgens to the testosterone receptor in various tissues, did not inhibit the DHT - induced decrease in the 3H-E2 uptake by the uterine nuclei or the DHT - caused accumulation of the estrogen receptor in nuclei. These results seem to indicate that the uterine testosterone receptor has no role in the androgen - induced nuclear uptake of the estrogen receptor. However, the non-steroidal antiestrogens inhibited the DHT - induced nuclear accumulation of the estrogen receptor. This would seem to indicate that the estrogen - and androgen - induced nuclear accumulation of the estrogen receptor share a common mechanism.

Androgens↗
PubMed1978

Inhibition by various steroids on dihydrotestosterone binding to androphilic protein in human benign prostatic hypertrophy.

The effect of various steroidal compounds on the binding of the androphilic protein to dihydrotestosterone in the cytosol of tissues of human benign prostatic hypertrophy was examined. Androgens, as well as estrogens and gestagens showed an inhibitory effect on the binding. Non-steroidal anti-androgens were revealed to be weak inhibitors on the binding. Two androphilic proteins were observed in Sephadex G-200 chromatography in fractions eluted at the void volume and in fractions appearing at the site of IgG, and the rate of inhibition on the binding of both fractions by various steroids was compared. The rate of inhibition by various compounds was generally higher in the IgG fraction than in the void volume fraction. When the ligand and inhibitors were incubated with the cytosol prior to fractionation by Sephadex chromatography, rate of inhibition was lower than that obtained when the ligand and inhibitors were reacted with fractions after chromatography. Implications of the difference observed in these two experiments are not clear at this moment. The results obtained by the protamine precipitation experiment were almost the same as those by the experiment using the extract of the unfractionated acetone-dried cytosol, therefore, the protamine procedure does not seem to precipitate the tissue specific androphilic protein specifically.

Androgens↗
PubMed1979

Regulation of cytosol and nuclear progesterone receptors in rabbit uterus by estrogen, antiestrogen and progesterone administration.

A synthetic progestin, 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione (ORG 2058), was utilized to measure progesterone receptors from the rabbit uterus. This steroid has a high affinity for both cytosol and nuclear receptors, with KD values of 1.2 nM (at 0--4 degrees C) and 2.3 nM (at 15 degrees C), respectively. Administration of estradiol-17 beta or a non-steroidal antiestrogen, tamoxifen, for 5 days to estrous rabbits led to a progressive rise in the cytosol receptor levels: from 34,000 to 120,000 (estradiol-17 beta) and 80,000 (tamoxifen) receptors/cell, without any major influence on the nuclear receptor content. A single intravenous injection of progesterone (5 mg/kg) elicited a 3-fold increase in the mean nuclear receptor content at 30 min after injection (from 18,000 to 48,000 receptors/nucleus). Nuclear receptor accumulation was short-lived and returned to control levels within 4 h after treatment. A second dose of progesterone given 24 h later doubled the nuclear receptor level (from 18,000 to 35,000 receptors/nucleus). The concomitant decline in the cytosol receptor content was twice that accounted for by the nuclear receptor accumulation (70,000 vs. 30,000, and 40,000 vs. 17,000 receptors/cell, after the first and second progesterone injection, respectively). Following progesterone administration, the cytosol receptor level reached a nadir by 30 min, exhibited minimal replenishment within the ensuing 24 h, and remained at approx. 50% of the pretreatment values. After a single dose or two consecutive doses of progesterone, total uterine progesterone receptor content declined to about 60% of the level prior to each dose, a nadir being reached at 2 h after treatment.

Animals↗