Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Norpregnadienes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the 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
PubMed1983

3H-estradiol and 3H-R5020 binding in cytosols of normal and neoplastic human ovarian tissue.

High-affinity cytoplasmic estrogen and progesterone receptors in normal and abnormal ovarian tissues were studied. Estradiol receptor was detectable in 65% and progesterone receptor in 36% of the malignant tumors; 39% of all malignant ovarian tissues were estradiol- as well as progesterone-receptor-positive. Tumors were said to be receptor-positive when the receptors bound greater than 5 fM steroid/mg cytosol protein. No correlations were found between receptor status and histopathological diagnosis. In normal ovarian tissues collected at various phases of the menstrual cycle no changes in [3H]-estradiol and [3H]-R5020 binding could be detected. Analysis of the receptor concentration for both steroid hormones with regard to the menopausal status demonstrated highest levels in postmenopausal women. No significant difference could be found when two groups of patients with advanced ovarian carcinoma associated with the cytosol estrogen receptor status were compared in terms of two different therapeutic schemes (cytosolic chemotherapy with and without tamoxifen).

Cytosol↗
PubMed1987

Difference between R5020 and the antiprogestin RU486 in antiproliferative effects on human breast cancer cells.

We have compared the effects of the progestin R5020 and the antiprogestin RU486 on the growth of the MCF-7 and T47D breast cancer cell lines. Differences between the two compounds were demonstrated in several parameters. 1. Estradiol was required for the efficient inhibition of cell growth of both lines by R5020 but not by RU486. Therefore in the total absence of estrogen (phenol-red free medium), the effects of the two drugs on cell growth were dissociated, RU486 remaining inhibitory while R5020 was inactive. 2. The proteins secreted by cells were differently affected, since R5020 induced a 48K protein and decreased the production of the estrogen-regulated 52K protein, while RU486 had no effect on these two parameters. 3. The morphology of cells treated by R5020 was more altered in the presence of estradiol than in its absence, while that of cells treated by RU486 was not affected whether or not estradiol was present. 4. There was a greater reduction of estrogen receptor sites in MCF-7 cells produced by R5020 than by RU486. Even though the two drugs appear to act through the same progesterone receptor and to inhibit total protein secretion, it is likely that they exert their antiproliferative effects on cultured breast cancer cells by different mechanisms. R5020 antagonizes the stimulation produced by estradiol. RU486 by contrast exerts a more direct progesterone receptor mediated inhibitory effect requiring no synergism by estradiol and therefore does not act through a partial progestin activity.

Breast Neoplasms↗
PubMed1980

Evidence for an unusual multifunctional protoreceptor in hormone action.

Contrary to the techniques of mere association, column chromatography has revealed a 'protoreceptor' that accepts aldosterone agonists and antagonists only in the physiological target, the kidney, and is absent in non-targets, liver and serum; it is furthermore different from the aldosterone specific receptor in renal cytosol.

Aldosterone↗
PubMed1995

Effects of an implant of nomegestrol acetate, a 19-nor-progesterone derivative, on thyroid function.

This study was undertaken to assess tri-iodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), T3 uptake, free T3 and free T4 in nomegestrol acetate implant (Uniplant) users. A total of eighteen volunteers of reproductive age who wanted to avoid conception were enrolled in the study. All subjects were investigated before starting treatment. Blood samples for hormonal analysis were taken prior to insertion of the implant. Thereafter, blood samples were drawn at 3, 6, 12, 18 and 24 months of Uniplant use. All subjects had used non-hormonal contraceptives for at least 6 months prior to insertion of the implant. The results observed in this study showed that there was no significant difference in tri-iodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) during two years of Uniplant use. No significant difference was found in free T3 levels during two years of Uniplant use. A significant decrease was observed in T3 uptake (p < 0.05) in month 24 and in free T4 (p < 0.05) in month 3 of Uniplant use. All changes observed in this study were inconsistent and all levels were within the normal range.

Adult↗
PubMed1980

Evidence for an androgen-binding component in the cytosol of the human term placenta.

The present communication describes a specific, high-affinity (Kd = 1.9 +/- 0.21 x 10(-9)M; n = 3) binding component for dihydrotestosterone present in the high-speed, hormone-stripped cytosol fraction of the human term placenta. In order to delineate the nature of this substance, the synthetic steroids R1881 (progesterone and androgen receptor specific) and R5020 (progesterone receptor specific) were employed. Minimal binding of H3-R5020 was observed; however, H3-R1881 was found to bind with a Kd = 0.6 +/- 0.18 x 10(-9)M (n = 3). The relative displacing ability of R5020 for H3-R1881 was only 1.3%, substantiating the presence of an androgen binder and negating the presence of a significant level of a progesterone-binding component. Evidence that the binder is of placental origin and does not result from blood contamination includes no significant binding of H3-R1881 to pregnancy serum, binder thermolability at 45 degrees C, and precipitation of the binder by ammonium sulfate at 30% saturation. Speculations as to the receptor or receptor-like nature of the binder are presented.

Binding, Competitive↗
PubMed1986

Effect of photoaffinity labeling on rabbit uterine progesterone receptor.

Photoaffinity labeling with [17 alpha-methyl-3H]promegestone ([ 3H]R5020) is an effective technique for the covalent labeling of the progesterone receptor (PR), which allows monitoring of the steroid receptor complex under denaturing conditions. The present study was initiated to evaluate whether photolabeled PR could be used also as a marker for PR under nondenaturing conditions. Accordingly, the effect of irradiation on each component of the reaction was evaluated separately. When [3H]R5020 alone was irradiated, there was a rapid (less than 5 min), light dependent destruction of [3H]R5020, as evident from increased formation of a more polar tritiated product on TLC and a concomitant decrease in the ability of the irradiated preparation to bind to PR. When rabbit uterine PR was irradiated in the absence of steroid, a gradual decrease in the binding capacity was observed, reaching 70% of the nonirradiated control in 10 min. The optimal irradiation time for covalent [3H]R5020-PR complex formation was determined by irradiation for up to 5 min, and separation of the products by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. Specific labeling of proteins of Mr 116,000 and 85,000 was observed, with the rate of labeling of the two being similar, and reaching a plateau by 4 min of irradiation. The photolabeling efficiency ranged from 2 to 12%. Sucrose gradient ultracentrifugation of photolabeled PR revealed that both the irradiated sample and the nonirradiated control sedimented to the same position. Subsequent SDS-polyacrylamide gel electrophoresis of the sucrose gradient peak from the photolabeled sample showed the presence of both labeled proteins of Mr 116,000 and 85,000. In addition, photolabeled rabbit uterine PR (Mr 116,000 and 85,000) could be immunoprecipitated with a guinea pig antiserum raised against rabbit uterine PR. Analysis of the photoaffinity labeling procedure in our system revealed that the photodestruction of [3H]R5020 was very rapid. However, maximal labeling with [3H]R5020 was obtainable with minimal photodestruction of PR which suggests that photolabeled receptor can be used as a marker for PR under nondenaturing conditions.

Affinity Labels↗
PubMed1983

Nuclear localization of a glucocorticoid antagonist in cultured hepatoma cells.

The binding characteristics of promegestone, a typical antagonist of glucocorticoid action, has been investigated. We localized [3H] promegestone in the nuclei purified from steroid-treated HTC cells but the radioactivity specifically bound to the nucleus was much lower for the antagonist than for an inducer steroid, for instance dexamethasone. We attempted to define the nature of the "nuclear" activity and found that promegestone does not bind to the perinuclear membrane but is associated with the chromatin fraction.

Animals↗
PubMed1985

A progestin effect on lactate dehydrogenase in the human breast cancer cell line T-47D.

The human breast cancer cell line T-47D has high levels of progesterone receptor even in the absence of exogenously added estrogen. Because of this it is a good line in which to study aspects of progestin action. It has been shown by others that lactate dehydrogenase in MCF-7 cells is responsive to estrogen but not to progesterone. Other proteins in other systems have been found to be responsive to both estrogen and progesterone, often requiring priming by estrogen, presumably to produce sufficiently high quantities of progesterone receptor. Reasoning that lactate dehydrogenase in T-47D cells might be stimulated by progestins alone at physiological levels since these cells already have high levels of progesterone receptor, we now report that this is indeed the case.

Breast Neoplasms↗
PubMed1985

The nuclear-bound form of the progesterone receptor is generated through a hormone-dependent phosphorylation.

The solubilized ("cytosolic") receptor present in the rabbit uterus in the absence of hormone and the chromatin-bound ("nuclear") receptor obtained after injection of a progestin were compared. Crude cellular extracts were analyzed by immunoblotting and receptors were purified by immunoaffinity chromatography. With both methods it was observed that the electrophoretic mobility of the "nuclear" receptor was slower than that of the "cytosolic" receptor. This difference in mobility appeared to be due to the existence of variably phosphorylated forms of receptor. The phosphorylation reaction was examined in uterine slices. In the absence of hormone the cytosolic receptor was phosphorylated. When hormone was added the phosphorylation of receptor was markedly enhanced and the electrophoretic mobility of the "nuclear" receptor was decreased. These experiments thus show that the receptor in its "cytosolic" form is a phosphoprotein. Under the effect of the hormone the receptor is further phosphorylated on some supplementary site(s). This polyphosphoprotein is the chromatin-bound, putatively active, form of the receptor. In this respect the intracellular progesterone receptor is similar to various membrane receptors for hormones and growth factors which are phosphorylated upon binding of their ligand.

Animals↗
PubMed1986

Antiprogestin-receptor complexes: differences in the interaction of the antiprogestin RU38,486 and the progestin R5020 with the progesterone receptor of human breast cancer cells.

In order to understand the molecular basis for antiprogestin action, we have compared the interaction of the antiprogestin [3H]RU38, 486 (RU486) and the progestin [3H]R5020 with the progesterone receptor (PR). In both MCF-7 and T47D human breast cancer cells, we have observed marked differences in the sedimentation properties of the PR on high salt sucrose gradients: while the R5020-receptor complexes sediment at approximately 4 S (4.4 +/- 0.1 S), the RU486-receptor sediments as a prominent 6 S species as well as a 4 S species. This binding is abolished by excess unlabelled R5020, RU486 or progesterone, but is unaffected by excess unlabelled hydrocortisone or dexamethasone, indicating that both the 4 S and 6 S species represent the PR and not glucocorticoid receptor. Although the relative distribution of 4 S and 6 S forms is not altered by treatment with DNAse or RNAse, exposure to 10 mM thioglycerol or to 3 M urea results in conversion of the 6 S to the 4 S form, suggesting that disulfide bonds and hydrophobic interactions are important in maintaining the integrity of the 6 S form. These findings suggest that the 6 S antiprogestin complex is formed as a result of the interaction of PR units with each other or with a different protein. This change in receptor association state may be an important aspect of the antiprogestin activity of RU486.

Binding, Competitive↗
PubMed1986

Progestin-induced down regulation of nuclear estrogen receptor in uterine decidual cells: analysis of receptor synthesis and turnover by the density-shift method.

The density-shift method was used to study the effect of the synthetic progestin, R5020, (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) on the turnover and synthesis of nuclear estrogen receptor in hamster decidual cells. Newly-synthesized receptor was labeled with dense [2H, 13C, 15N] amino acids and separated from pre-existing receptor by density-gradient centrifugation. Progestin increased receptor turnover within 3 h of treatment and blocked estradiol-induced receptor synthesis at 6 h and 9 h. Thus, progestin down regulates estrogen receptor by increasing receptor turnover and inhibiting estrogen-induced receptor replenishment.

Animals↗
PubMed1987

Progestin effects on growth in the human breast cancer cell line T-47D--possible therapeutic implications.

In order to determine growth effects of the progestin R5020, (promegestone), we have utilized the progesterone-receptor rich human breast cancer cell line T-47D, growing the cells in the absence of the pH indicator phenol red, which has recently been found to be estrogenic. In contrast to reports on cells grown in the presence of phenol red, we find that promegestone alone, at physiological progestin concentration, significantly stimulates growth. Estradiol alone, at physiological concentration, stimulates growth much more. Promegestone in combination with estradiol is antiestrogenic for growth; that is, it significantly decreases the growth stimulatory effect of estradiol. These results raise the possibility that estrogen receptor and progesterone receptor-rich breast cancer patients might benefit more from a combination of anti-progestin and anti-estrogen therapy than from anti-estrogens alone.

Breast Neoplasms↗