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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although in vivo effects of 17 beta-estradiol (estrogen) on bone turnover have been shown to occur mainly through influences on osteoclast-mediated bone resorption, the mechanism by which estrogen reduces bone resorption is unclear. To approach this question, we have examined authentic osteoclasts for evidence of a direct osteoclast response to estrogen in vitro. Highly purified (greater than (90%) viable avian osteoclasts from birds maintained on a low calcium diet were obtained using an osteoclast-specific monoclonal antibody coupled to magnetic beads. Isolated cells were either analyzed directly for estrogen receptor (ER) levels or cultured to assess the biological effects of estrogen. Northern blot analysis revealed a 5.2-kilobase mRNA that hybridized with a cDNA to human ER mRNA in the osteoclasts. An anti-human ER antibody recognized proteins of 66 kDa and 140 kDa in osteoclast extracts by Western blot analysis. The 66-kDa size is in close agreement with the reported size of the human ER. Nuclear binding of estrogen to intact viable osteoclasts was steroid-specific and saturable, with 5662 +/- 1420 molecules bound per nucleus (mean +/- SEM). In vitro estrogen responses in osteoclasts included a dose-dependent decrease in resorption as well as an increase in nuclear protooncogene mRNA levels. These observations indicate that osteoclasts are capable of directly responding to estrogen in vivo.
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PMID:Avian osteoclasts as estrogen target cells. 190 73

This paper addresses the expression of the epidermal growth factor (EGF) gene by human breast tumor biopsy samples. Northern analysis was used to demonstrate the presence of an approximately 5-kilobase mRNA which specifically hybridized with radiolabeled human EGF complementary DNA in some human breast tumor biopsy samples. Quantitation of EGF mRNA in 60 human breast tumor biopsies using the RNase protection assay revealed that 83% of tumors contained detectable EGF mRNA. Estrogen receptor (ER) and progesterone receptor (PgR) mRNAs were similarly quantitated in the same samples. It was found that 89.4% of the ER mRNA-positive breast tumor biopsies had detectable EGF mRNA, whereas only 58.3% of the ER mRNA-negative tumors had detectable EGF mRNA. Furthermore, whereas 90.5% of the PgR mRNA-positive tumors contained EGF mRNA, only 60% of the PgR mRNA-negative tumors contained EGF mRNA. chi 2 analysis indicated that the increased percentage of tumors expressing EGF in the receptor-positive groups was statistically significant (P less than 0.01). It was also found that the mean relative level of EGF mRNA in those tumors which were ER and PgR negative [9.8 +/- 5.6 (SEM) relative units] was significantly lower than those tumors which were ER and PgR positive (40.5 +/- 6.4 relative units, P less than 0.05) or ER positive and PgR negative (68.4 +/- 19.9 relative units, P less than 0.005). These observations suggest that the EGF-expressing tumors probably arose originally from hormonally responsive cell types and that EGF expression in a large proportion of human breast tumors in vivo may also be hormonally responsive.
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PMID:Epidermal growth factor gene expression in human breast cancer biopsy samples: relationship to estrogen and progesterone receptor gene expression. 236 77

The estrogen receptor (ER)-positive human breast cancer cell line T 47D exhibited genetic instability under cell culture conditions which maintained almost continuous exponential growth. This resulted in the spontaneous generation of three ER-positive sublines with a range of DNA ploidies and distinctive phenotypes. One of these sublines, T 47D-5, exhibited resistance to the growth-inhibitory effects of the synthetic nonsteroidal antiestrogen tamoxifen and the synthetic progestin ORG 2058, in marked contrast to "wild type" T 47D cells (designated T 47D-7 in this study). T 47D-5 cells were cloned by limiting dilution and 11 clonal cell lines were tested for sensitivity to tamoxifen. Although all clones of T 47D-5 were significantly less sensitive than T 47D-7 cells, a spectrum of sensitivities was observed. Three clones, T 47D-5-13, T 47D-5-21, and T 47D-5-23, were further characterized by measuring the concentrations of receptors for estrogen, progesterone, growth hormone, and epidermal growth factor and responses to estradiol, tamoxifen, and progestin, in terms of both induction of specific proteins and effects on cellular proliferation. Although the T 47D-5 subline and clone T 47D-5-23 were insensitive to both the growth-stimulatory effects of estradiol and the inhibitory effects of tamoxifen, this was not related to the concentration of ER or its ability to induce progesterone receptor. Estrogen receptor levels were similar in resistant and sensitive clones of T 47D-5 [70,000-81,000 sites/cell] and were 2.5-fold greater than in the sensitive T 47D-7 line [32,600 +/- 5,000 (SEM) sites/cell]. Northern blots showed no difference in the size of ER mRNA transcripts between sensitive and resistant clones. Estradiol treatment increased progesterone receptor (PR) levels in all cell lines but the magnitude and sensitivity of this response were unrelated to growth responses indicating a divergence in estrogenic control of cellular proliferation and specific protein synthesis within these clones. T 47D-5, T 47D-5-13, T 47D-5-21, and T 47D-5-23 were all insensitive to the growth-inhibitory effects of ORG 2058. The progestin was also unable to increase lactogenic and epidermal growth factor receptor concentrations in these four lines in contrast to the response in T 47D-7 cells. The insensitivity to progestin in the T 47D-5 subline and its three clonal cell lines could be accounted for, in part, by a 75-80% reduction in PR levels when compared with T 47D-7 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. 339 Aug 30

Although osteoporosis is usually associated with women, 1 in 12 men in the UK have the disease, and a third of these cases are idiopathic. Estrogen is now known to be associated with bone loss in older men, but we found, previously, that levels of this hormone were normal in younger cases of male idiopathic osteoporosis (MIO) in the age range 33-61 years. We therefore hypothesized that their estrogen responses in bone might be defective, through impaired estrogen receptor-alpha (ER)-alpha expression. Consequently, in the present study, we compared expression of ER-alpha by indirect immunofluorescence, semiquantitative image analysis, and in situ reverse transcription-polymerase chain reaction in bone sections from MIO patients (33-56 years) (N = 7); age-matched control men (N = 7); and, for reference, ovarian steroid (OS)-replete (N = 7) and OS-deficient women (N = 6). In the control men, 23 +/- 6% (mean +/- SEM) of osteoblasts and 14 +/- 2% of osteocytes expressed ER-alpha protein, similar to OS-replete women. Although receptor expression decreased in OS-deficient women, the loss of ER-alpha protein in MIO patients was more severe (1 +/- 0.5% osteocytes, 2 +/- 1% osteoblasts expressed receptor); however, ER-alpha messenger RNA (mRNA) was still expressed in controls and MIO patients. Bone loss in these patients may be due to deficient ER-alpha protein expression.
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PMID:Preliminary evidence for impaired estrogen receptor-alpha protein expression in osteoblasts and osteocytes from men with idiopathic osteoporosis. 1077 80

Feedback regulation of luteinizing hormone-releasing hormone (LHRH) neurons by estradiol plays important roles in the neuroendocrine control of reproduction. Recently, we found that the majority of LHRH neurons in the rat contain estrogen receptor-beta (ER-beta) mRNA, whereas, they seemed to lack ER-alpha mRNA expression. In addition, we observed nuclear uptake of (125)I-estrogen by a subset of these cells. These data suggest that ER-beta is the chief receptor isoform mediating direct estrogen effects upon LHRH neurons. To verify the translation of ER-beta protein within LHRH cells, the present studies applied dual-label immunocytochemistry (ICC) to free-floating sections obtained from the preoptic area of rats. The improved ICC method using the silver-gold intensification of nickel-diaminobenzidine chromogen, enabled the observation of nuclear ER-beta-immunoreactivity in the majority of LHRH cells. The incidence of ER-beta expression was similarly high in LHRH neurons of ovariectomized female (87.8 +/- 2.3%, mean +/- SEM), estradiol-primed female (74.9 +/- 3.2%) and intact male (85.0 +/- 4.7%) rats. The presence of ER-beta mRNA, ER-beta immunoreactivity and (125)I-estrogen binding sites in LHRH neurons of the rat provide strong support for the notion that these cells are directly regulated by estradiol, through ER-beta. The gene targets and molecular mechanisms of this regulation remain unknown.
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PMID:Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain. 1141 51