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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin suppresses growth hormone expression and induces prolactin (PRL) biosynthesis in MtT/S cells cultured in a medium supplemented with normal sera. Incorporation of [35S]amino acids into immunoprecipitable PRL became detectable at 15 h of culture with insulin (500 ng/ml) and increased up to 48 h. Northern blot hybridization demonstrated a concurrent induction of PRL mRNA. However, insulin failed to induce PRL in a medium supplemented with steroid-depleted sera. Either pre- or cocultivation of cells with 10 pM to 10 nM 17 beta-estradiol (E2), which did not induce PRL by itself, restored the insulin-mediated PRL biosynthesis in a dose-dependent manner. Diethylstilbestrol was as effective as E2, whereas testosterone, progesterone and corticosterone were without effect. The E2 action was partially suppressed by tamoxifen. These results suggest that estrogen is required for the insulin-mediated induction of PRL biosynthesis in MtT/S cells.
Mol Cell Endocrinol 1991 Dec
PMID:Estrogen-insulin synergism in induction of prolactin in growth hormone-producing cells. 179 11

Estrogen causes the cytoplasmic destabilization of albumin and gamma-fibrinogen mRNA in Xenopus laevis liver. The purpose of the present study was to determine whether mRNA destabilization is a generalized phenomenon in response to estrogen, or whether this process is restricted to a particular class of mRNAs. To address this, we have expanded our bank of serum protein-coding cDNA clones to include transferrin, the second protein of inter-alpha-trypsin inhibitor and clone 12B, for which there is no mammalian homolog. Together with albumin and gamma-fibrinogen, these represent more than 85% of the mRNAs encoding liver secreted proteins. Estrogen administration to male Xenopus or to liver explant cultures causes the generalized disappearance of all of these mRNAs. In contrast, estrogen has no effect on actin, ferritin, or poly(A)-binding protein mRNA, all of which encode intracellular proteins. We have previously demonstrated that albumin mRNA is degraded in both messenger ribonucleoprotein and polysome fractions. Sucrose gradient analysis demonstrates the same pattern for degradation of all other serum protein-coding mRNAs. Estrogen has no effect on the amounts or gradient distribution of actin, ferritin, or poly(A)-binding protein mRNA. We conclude that regulated destabilization of mRNAs encoding secreted proteins is a generalized phenomenon in response to estrogen stimulation of Xenopus liver.
Mol Endocrinol 1991 Apr
PMID:Coordinate estrogen-regulated instability of serum protein-coding messenger RNAs in Xenopus laevis. 192 78

The phosphatidyl inositol (PI) second messenger pathway may mediate diverse effects of estrogen, including its potentiation of the effects of other hormones. Both estradiol (E2) and luteinizing hormone-releasing hormone (LHRH) induce a putative isoform of PI-specific phospholipase C-alpha (PLC-alpha). PLC-alpha catalyzes PI hydrolysis, which in turn can increase protein kinase C (PKC) activation, Ca2+ mobilization, and arachidonic acid metabolism. Estrogen activates the PI pathway, and components of the PI pathway can mimic or enhance some effects of estrogen. Furthermore, estrogen potentiates effects of several hormones (e.g., LHRH, prolactin, and insulin) which can also act through the PI system. PLC-alpha may therefore provide a common second messenger pathway mediating the potentiation by E2 of the effects of other hormones; in addition it may also mediate some or all of the many actions of E2, since components of the PI pathway can have secretory, trophic, toxic, and neuromodulatory effects.
Mol Cell Endocrinol 1991 Sep
PMID:PLC-alpha: a common mediator of the action of estrogen and other hormones? 195 69

In contrast to the effects observed in vivo, isolated uterine cells cultured in vitro demonstrate little proliferative response to estrogens. Estrogen induced uterine proliferation involves a carefully orchestrated, sequential activation of genes which encode a variety of biologically active molecules. These include nuclear transcription factors, growth factors and growth factor receptors. Expression of these proteins serve to amplify the effect of estrogen through cellular, autocrine and paracrine mechanisms. In this review the effects of estrogen on uterine expression of the myc family of oncogenes and the insulin-like growth factors are discussed.
J Steroid Biochem Mol Biol 1991
PMID:Estrogen induction of insulin-like growth factors and myc proto-oncogene expression in the uterus. 195 25

Estrogen synthesis by aromatase occurs in a number of tissues throughout the body. Strategies which reduce production of estrogen offer useful means of treating hormone-dependent breast cancer. Initially, several steroidal compounds were determined to be selective inhibitors of aromatase. The most potent of these, 4-hydroxyandrostenedione (4-OHA) inhibits aromatase competitively but also causes inactivation of the enzyme. A number of other steroidal inhibitors appear to act by this mechanism also. In contrast, the newer imidazole compounds are reversible, competitive inhibitors. In vivo studies demonstrated that 4-OHA inhibited aromatase activity in ovarian and peripheral tissues and reduced plasma estrogen levels in rat and non-human primate species. In rats with mammary tumors, reduction in ovarian estrogen production was correlated with tumor regression. 4-OHA was also found to inhibit gonadotropin levels in animals in a dose-dependent manner. The mechanism of this effect appears to be associated with the weak androgenic activity of the compound. Together with aromatase inhibition, this action may contribute to reducing the growth stimulating effects of estrogen. A series of studies have now been completed in postmenopausal breast cancer patients treated with 4-OHA either 500 mg/2 weeks or weekly, or 250 mg/2 weeks. These doses did not affect gonadotropin levels. Plasma estrogen concentrations were significantly reduced. Complete or partial tumor regression occurred in 26% of the patients and the disease was stabilized in 25% of the patients. The results suggest that 4-OHA is of benefit to postmenopausal patients who have relapsed from prior hormonal therapies. Several of the steroidal inhibitors are now entering clinical trials as well as non-steroidal compounds which are more potent and selective than aminoglutethimide. Aromatase inhibitors should provide several useful additions to the treatment of breast cancer.
J Steroid Biochem Mol Biol 1991
PMID:Aromatase and its inhibitors--an overview. 195 29

In a previous paper (J. Steroid Biochem. 29 (1988) 475-480), the isolation of a 17 kDa protein that was dramatically induced in the uterus of estrogen-treated spayed rats was presented. We now describe a new purification procedure that is compatible with microsequencing of the 17 kDa protein. The protein partial N-terminal amino acid sequence analysis gave 28 residues that revealed a strong homology to the human major basic protein (MBP) of eosinophils described by Wasmoen et al. (J. Biol. Chem. 263 (1988) 12559-12563). Polyclonal rabbit antibodies were raised against this protein and used for tissue or blood cell analysis after electrophoresis and Western blotting. The 17 kDa protein was found to be constitutively present in the stomach and small intestine of the rat and guinea-pig. Estrogen treatment had a clearcut effect in guinea-pig uterus, but not as drastic as that observed in rat uterus. The protein was abundant in purified rat eosinophils. The antibodies cross-reacted with human MBP and an equivalent molecular weight human polymorphonuclear leukocyte protein. Immunohistochemical staining of rat uterus sections showed that the protein was first only associated with eosinophils that emigrate upon estrogen treatment; it then spread throughout the stroma and the deep glandular epithelium. It was not found in the myometrium. In conclusion, the appearance of a 17 kDa protein that is presumably the rat MBP is clearly regulated in the rat uterus.
J Steroid Biochem Mol Biol 1991 Mar
PMID:Identification and tissue localization of an eosinophil 17 kDa protein accumulating in rat uterus upon estradiol treatment. 200 23

We have characterized further the heterogeneous nuclear-specific doublet forms of the mouse uterine estrogen receptor (ER). Estrogen treatment produced the multiple nuclear ER forms of 65 and 66.5 kDa, which were isolated and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Soluble ER preparations exhibited only a single 65-kDa form. Isolation of the individual nuclear ER forms and reanalysis demonstrated that formation of the multiple bands was not due to artifacts of nuclear sample preparation or the presence of contaminating proteins. Analysis of individual uterine cell types (epithelial and stromal/myometrium) indicated that both ER forms were present in both cell fractions. Fractionation of nuclear components with low salt showed that both ER forms were found in the salt-resistant fraction. Extraction of nuclei with high salt (0.6 M KCl) solubilized both ER forms. Phosphorylation was studied as a protein modification to account for the multiple forms. Incorporation of 32P into uterine protein both in vivo and in intact tissue incubation indicated 32P labeling of uterine nuclear ER after hormone treatment. Both nuclear ER forms are labeled, although the 66.5-kDa form appears to be more heavily labeled. Phosphoamino acid analysis of the immunopurified 32P-labeled ER from intact uterine tissue indicated phosphoserine as the only phospholabeled residue. These data suggest that phosphorylation is associated with the physiological functioning of the ER in response to hormone and produces the heterogeneous ER forms in the nucleus.
Mol Endocrinol 1991 Feb
PMID:Uterine estrogen receptor in vivo: phosphorylation of nuclear specific forms on serine residues. 203 45

Progesterone enhances the synthesis of a 42 kDa protein secreted by rabbit endometrial stromal cells in primary culture. The duration of that response, the effects of estrogen and the inhibitory ability of antiprogestin steroid analogs, RU486, ZK98.299 and ZK98.734, were tested. Although there was a progressive decrease in the amount of the 42 kDa protein synthesized during a 6-day culture period, progesterone stimulated its rate of synthesis greater than 2-fold throughout that period. The addition of estrogen did not prevent the progressive decrease in the amount of the protein synthesized, nor did it enhance the progesterone effect when the culture medium contained phenol red. Estrogen alone did slightly induce 42 kDa protein synthesis by cells grown in phenol red-free medium, and the progesterone response was accentuated to the same degree. When present in a concentration that was 100-fold that of the progesterone, RU486, ZK98.299 and ZK98.734 each abolished stimulation. This antagonistic effect was overcome by addition of an equimolar concentration of progesterone. Deoxycorticosterone (DOC) also stimulated 42 kDa protein synthesis. The antiprogestins blocked this stimulatory effect, even when both steroids were in equimolar concentrations. There was no difference in the ability of ZK98.299 or ZK98.734 to block DOC stimulation, even though ZK98.734 exhibits no antiglucocorticoid activity [J. Steroid Biochem. 25 (1986) 835]. Therefore, it is likely that the DOC effect is mediated by the progesterone receptor system. These studies indicate that enhanced synthesis of the 42 kDa protein represents a progesterone receptor mediated event and that the cell culture system described can be used as a bioassay for determination of antiprogestin activity.
J Steroid Biochem Mol Biol 1991 Jul
PMID:Effects of progestin antagonists, glucocorticoids and estrogen on progesterone-induced protein secreted by rabbit endometrial stromal cells in culture. 206 62

The conversion of estrone sulfate (E1S) to estrone (E1) was measured during the in vitro incubation of the labeled sulfoconjugate with implantation sites (IS) and nonimplanted regions (NIS) of uterine horns from 6-day pregnant rats. Extensive metabolism of E1S occurred in both tissues, being noticeably less (29.31%) in IS than in NIS. Estrogen sulfatase activity present in the uterus of ovariectomized virgin rats was found to be higher than in both uterine regions of the pregnant rats. We suggest that E1S present in uterine fluids may be accessible to be metabolized into unconjugated estrogens by both intrauterine tissues of 6-day pregnant rats. This metabolism could be locally modulated in IS through the participation of the estrogen sulfatase, the activity of which is in turn controlled by the presence of free estrogens, possibly synthesized and/or secreted by the embryo, which has been shown to inhibit the sulfohydrolase activity.
J Steroid Biochem Mol Biol 1991 Jul
PMID:Uterine estrogen sulfatase activity at the time of blastocyst implantation in the rat. 206 64

The activity of poly (ADP-ribose) polymerase (ADPRP) and the content of 2',5'-oligodenylates core (2',5'An; n = 2,3 and 4) were measured in homogenates of the uterus and of the liver of immature rats immediately before (time 0) or at different times after injection of estradiol-valerate. ADPRP activity increased gradually, starting 6 hours after estrogen injection, for about 4 days. Instead, the content of 2',5'An decreased by about 50% within 6 hours, and thereafter more slowly for 4 days to about 20% of starting values. Estrogen increased ADPRP activity and decreased 2',5'An concentration also in the kidney and in the cardiac muscle of the same animals, but not in the skeletal muscle, where neither of the two parameters was affected. Injection of vehicle only (sesame oil) had no effect on ADPRP activity nor on 2',5'An content of immature rat tissues.
Mol Cell Biochem 1990 Dec 03
PMID:Inverse relationship between poly (ADP-ribose) polymerase activity and 2',5'-oligoadenylates core level in estrogen-treated immature rat. 212 38


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