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

Estrogen is thought to stimulate the proliferation of human breast tumors indirectly, through induced production of autocrine polypeptide growth factors. Constitutive production of such growth factors would lead to the loss of 17 beta-estradiol (E2)-dependence that is associated with progression of the disease. Our data, however, do not support this hypothesis and suggest that hormone-dependent breast tumor cell lines like MCF7 do not react to the growth factors which they produce. Moreover, we provide evidence that E2 directly stimulates proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic. This may be caused by the lack of induction of genes from the jun family, whose gene products are necessary for dimerization with the c-fos encoded protein, leading to an important step in growth factor signalling pathways; stimulation of TPA responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors, efficient inducers of c-jun in these cells, E2 synergistically stimulates proliferation and TRE-activity. Constitutive TRE-activation may lead to loss of E2-dependence.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Direct stimulation by estrogen of growth factor signal transduction pathways in human breast cancer cells. 152 51

The effects of 17 beta-estradiol versus tamoxifen on the growth and metabolism of MCF7 human breast cancer cells, in culture and in tumors implanted in nude mice, were studied by 31P and 13C nuclear magnetic resonance spectroscopy and by proton magnetic resonance imaging. In culture, the content of the phosphate metabolites including nucleoside triphosphates (NTP), phosphomonoesters, phosphodiesters and inorganic phosphate (Pi) were not affected by tamoxifen treatment. However, in the presence of estrogen the rate of glucose consumption and lactate production via glycolysis (270 and 280 fmol/cell.h, respectively) were twice that of tamoxifen treated cells. Estrogen rescue of tamoxifen treated cells indicated that glycolysis induction occurs at the early stages of the hormonal response. The in vivo studies included recording of proton images that provided an accurate measure of tumor size and distribution of tumor cells, necrotic regions and stromal tissue. Tamoxifen caused enhanced necrosis extending from the center of the tumor during the first two days of treatment (12 h to 6 days). This was followed by growth of reparative tissue along with tumor regression. Tamoxifen also modified the content of the phosphate metabolites, increasing markedly (P less than 0.0002) the ratio of NTP to Pi from 0.41 before treatment to 1.75 9-19 days after treatment. This change was attributed to the enhanced growth of repair tissue. The results provide new information regarding the response of human breast cancer to hormonal treatment and suggest a mechanism for the induction of tumor regression by tamoxifen.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging. 152 59

We have previously demonstrated the existence of nuclear estrogen receptors in isolated adipocytes (Pedersen et al. (1991) Biochim. Biophys. Acta 1093, 80-86). In the present study we have investigated the regulatory properties of these nuclear estrogen receptors, in addition to the metabolic effects of estrogen on adipose tissue metabolism. Estrogen treatment (20 micrograms 17 beta-estradiol in NaCl for 7 days) decreased lipoprotein lipase activity (LPL) in the adipose tissue by 62% (p less than 0.05), decreased adipocyte size by 27% (p less than 0.01) and diminished the normal postovariectomy weight gain. Furthermore, estrogen treatment increased the nuclear estrogen receptor binding in adipocytes; in addition, there was a tendency for increased cytosolic estrogen receptor content as well. Time course studies revealed that already 6 h after a single estrogen injection the Bmax increased from 3.82 +/- 0.3 fmol/10(6) cells to 9.8 +/- 3.6 fmol/10(6) cells (p less than 0.1) and 24 h after a single injection the Bmax was maximally increased to 12.7 +/- 5.5 fmol/10(6) cells (p less than 0.05). The Kd was similar at all time points (about 3-5 nM). Furthermore, the specific insulin receptor binding was increased in adipocytes from estrogen treated rats. The specific insulin binding was maximally increased by 149 +/- 6% (p less than 0.001) after 4 days of daily estrogen injections. The increased binding seemed to be due to an increased number of insulin receptors on adipocytes from estrogen treated rats with no alteration of the ED50 value. In conclusion it was found that estrogen treatment has a positive feedback effect on its own nuclear receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 May
PMID:Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes. 152 13

An in situ hybridization method using paraffin-embedded sections was used to characterize the chicken oviduct cells synthesizing ovalbumin mRNA due to the action of estrogen and progesterone. The cytodifferentiation of the oviduct cells was induced by 17 beta-estradiol administration to newly hatched female chicks. To avoid possible effect of estrogen on the action of progesterone the chicks were withdrawn from the estrogen by six days withdrawal period without hormone treatment. Ovalbumin mRNA was not synthesized after a period of estrogen withdrawal. Administration of estrogen induced ovalbumin mRNA in the tubular gland cells. Administration of progesterone induced the expression of ovalbumin mRNA in the surface epithelial cells. It was also found that progesterone induced mucus producing goblet cells in the surface epithelium. Estrogen did not have an effect on the mucus production, which suggests that progesterone could induce the terminal differentiation of the goblet cells. We conclude that the expression of ovalbumin in the surface epithelial cells and in the tubular gland cells is specific for progesterone and estrogen, respectively.
J Steroid Biochem Mol Biol 1992 Mar
PMID:In situ hybridization of ovalbumin mRNA in the chick oviduct reveals target cell specificity for estrogen and progesterone. 156 35

In addition to effects on brain protein synthesis, neurotransmitter release, and electrophysiology, estrogens alter neurite outgrowth and synaptogenesis. This study examined in the adult rat the effects of estrogen and sex on the expression of the GAP-43 gene; encoding a phosphoprotein structurally and physiologically linked to these two processes in the rat CNS. Ovariectomized (OVX) rats were injected with vehicle or estrogen, or male and female rats were either gonadectomized or left intact. Brains were dissected to obtain ventromedial hypothalamus (VMH), posterior hypothalamus (PH), or frontal cortex (CTX). Total RNA from these areas were extracted, and slot-blots of equal masses of total RNA were hybridized to 32P-labeled cDNAs for GAP-43 and beta-actin, and also to synthetic poly-dT. Resultant autoradiograms were scanned by laser densitometry, quantitated, and ratios of the gray scale generated by each probe were compared between experimental groups. GAP-43 mRNA expression, when compared to expression of either beta-actin mRNA or total poly(A)-containing RNA (poly(A) RNA), was higher in VMH and PH as compared to CTX. Estrogen treatment of OVX rats resulted in a 48-74% increase in GAP-43 mRNA levels in the VMH--in one experiment, this increase was noted after 2 h of estradiol treatment, and in another after 3 days of estradiol benzoate treatment; but PH and CTX were unaffected by either estrogen regimen. Conversely, ovariectomy of intact rats decreased GAP-43 mRNA expression by 45% in the VMH, but not in the CTX.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1991 Sep
PMID:Estrogenic regulation and sex dimorphism of growth-associated protein 43 kDa (GAP-43) messenger RNA in the rat. 166 9

Serum levels of total 1,25-dihydroxyvitamin D (1,25(OH)2D), vitamin D binding protein (DBP), sex hormone binding globulin (SHBG), testosterone, estradiol 17 beta (E2) and the "free" 1,25(OH)2D index were measured before and during treatment in prostatic cancer patients treated by orchidectomy (n = 15), with combined i.m. polyestradiol phosphate (PEP) + oral ethinyl estradiol (EE) (n = 10) and with i.m. PEP only for 3 months, followed by addition of oral EE (n = 9). Total concentrations of 1,25(OH)2D and DBP were unaffected by orchidectomy and treatment with i.m. PEP only, but were significantly elevated during treatment including oral EE. SHBG levels were unaffected by orchidectomy, slightly increased by i.m. PEP only and greatly increased by oral EE. The free 1,25(OH)2D index was slightly elevated by treatment including oral EE. Evidence was obtained that the increase in 1,25(OH)2D levels observed during oral estrogen treatment was secondary to the estrogen-augmented increase in DBP and not a result of an estrogen-stimulated synthesis of 1,25(OH)2D. Furthermore, the stimulatory effect of estrogen on DBP concentrations seemed to be dependent on the route of administration of the hormone.
J Steroid Biochem Mol Biol 1991 Aug
PMID:Effects of orchidectomy and different modes of high dose estrogen treatment on circulating "free" and total 1,25-dihydroxyvitamin D in patients with prostatic cancer. 188 74

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


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