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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen deficiency is well recognized as a cause of bone loss in rats and humans. Likewise, treatment with estrogen results in prevention of this loss. Initially, this effect was thought to be indirectly mediated but, more recently, estrogen receptors (ER) have been reported in osteosarcoma cells and primary cultures originating from surgical waste, suggesting a direct effect of this steroid hormone. Detection of ER in skeletal tissues, however, has remained elusive. The purpose of this investigation was to establish the efficacy of the highly sensitive reverse-transcription polymerase chain reaction (RT-PCR) technique to detect ER in a well defined skeletal tissue (calvarial periosteum) that is responsive to the hormone. Primers were made specific to rat ER sequences. Total RNA was extracted from rat uterus, liver, spleen, and the periosteum using an organic solvent method. cDNA was synthesized from 2 micrograms total RNA. cDNA corresponding to 40 ng total RNA/sample produced intense PCR products for ER. In descending order of intensity were uterus, liver, bone, and spleen. Importantly, a similar time-course for estrogen-induced down-regulation of steady-state mRNA levels for alkaline phosphatase and osteonectin was observed in calvarial periosteum and tissues known to express estrogen receptors. These data provide in vivo evidence of ER mRNA in bone and suggest that at least some of estrogen's action on bone is directly modulated.
Steroids 1995 Jul
PMID:Estrogen receptor mRNA is expressed in vivo in rat calvarial periosteum. 748 34

The interrelationship between estrogen and insulin-like growth factor-I (IGF-I) in the regulation of uterine growth was studied in the rat. The levels of the estrogen receptor (ER), ER mRNA, and IGF-I mRNA in rat uterus and liver were monitored. Uterine ER in normal cycling rats was highest in proestrus and diestrus, as was IGF-I mRNA. ER mRNA and plasma estradiol peaked in proestrus. Hepatic ER mRNA and IGF-I mRNA were highest in diestrus, whereas ER was not significantly changed during the estrous cycle. The temporal effects of multiple injections or continuous infusion of 17 beta-estradiol in ovariectomized rats were examined. In the uterus of animals subjected to multiple injections, a 10-fold increase in IGF-I mRNA was seen 24 h after the start of the treatment, whereas rats given continuous infusion of estradiol showed a more than 16-fold increase. In both groups, the increase of IGF-I mRNA was transient although estrogen treatment was continued. To study local hormonal effects, ovariectomized rats were given estradiol in vaginal implants. The uterine IGF-I mRNA level increased two-fold in 3 days. The ER mRNA level increased 1.5-fold and the uterine weights were doubled. The plasma estradiol concentration did not change during the treatment. A separate experiment was carried out to establish whether IGF-I itself exercises estrogen-like effects. Ovariectomized rats were given hrIGF-I in osmotic minipumps for 3 days. The uteri of the treated animals weighted significantly more than did the controls. Quantitation of the level of uterine estrogen receptors revealed a significant decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1994 Jul
PMID:Estrogen regulation of the estrogen receptor and insulinlike growth factor-I in the rat uterus: a potential coupling between effects of estrogen and IGF-I. 797 26

Two 11 beta-derivatives of estradiol (E2) were tested for their potential antiestrogenic activity in the MCF-7 breast cancer model: one contained a phenoxydimethylaminoethyl side-chain (RU 39,411), the other a pentafluoropentylsulfinyl side-chain (RU 58,668). The former compound displayed mixed estrogenic/antiestrogenic properties, while the latter indicated only an antiestrogenic activity. Both the compounds produced a growth inhibition of MCF-7 cells at doses related to their binding affinity for the estrogen receptor (ER); E2 suppressed this inhibition. The compounds also down-regulated the estrogen binding capacity of the cells but failed to reduce ER mRNA levels, indicating that the grafting of their side-chains prevented this antagonistic effect usually observed with steroidal estrogens. Assessment of ER levels by enzyme immunoassay revealed a marked increase with RU 39,411 and a decrease with RU 58,668; different mechanisms of action should, therefore, be considered. Finally, the estrogenic activity of RU 39,411 was demonstrated by its strong ability to induce synthesis of the progesterone receptor; RU 58,668 failed to display this agonistic activity.
Steroids 1995 Aug
PMID:Antiestrogenic activity of two 11 beta-estradiol derivatives on MCF-7 breast cancer cells. 853 93

The recent cloning of a second form of the estrogen receptor (ER-beta) has made it possible to map the distribution of ER-beta mRNA-containing perikarya in the rat hypothalamus. The present in situ hybridization histochemical studies have detected ER-beta mRNA in the medial preoptic area; the anterior periventricular, paraventricular, supraoptic, arcuate, medial tuberal and medial mammillary nuclei; the bed nucleus of the stria terminals, and zona incerta. As previously described for the classical ER (ER-alpha) mRNA, a dense accumulation of ER-beta mRNA-expressing perikarya is present in the medial preoptic area and bed nucleus of the stria terminalis. In contrast, ER-beta mRNA was also concentrated in the paraventricular and supraoptic nuclei, brain regions which contain little or no ER-alpha mRNA. Moreover, the arcuate and ventromedial nuclei, areas with abundant ER-alpha. contain only a weak level of ER-beta hybridization signal. The description of ER-beta mRNA-containing perikarya in the rat hypothalamus provides a foundation for further morphological and physiological studies aimed at elucidating the role of ER-beta in the hypothalamus.
Steroids 1996 Dec
PMID:The distribution of estrogen receptor-beta mRNA in the rat hypothalamus. 898 35

Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation.
Steroids 1997 Oct
PMID:Hormonal regulation of the estrogen receptor in primary cultures of hepatocytes from female rats. 938 11

Several reports have shown an interaction between the estrogen receptor (ER) and the protein kinase C (PKC) intracellular pathways. Data from our laboratory showed that PKC activation can modulate ER levels and responsiveness in estrogen target tissues such as uterus and bone. In particular, ROS.SMER #14 osteoblastic cells, stably transfected with the mouse ER, undergo specific morphological changes in vitro. ROS.SMER #14 cells at post-confluence express a differentiated phenotype and become unresponsive to estrogenic stimulation. Interestingly, ER mRNA and protein levels were not modified by post-confluence, but ER binding sites/cell (2500-3000/cell at subconfluence) were undetectable. Moreover, PKC activity was significantly increased in post-confluent cells. Inhibition of PKC by H7 or staurosporin (PKC inhibitors) or down-regulation by long-term treatment with 12-O-tetradecanoylphorbol-13-acetate enchanced ER binding capacity in a dose-dependent manner. Since the PKC family includes several different isoforms that play different roles in cell homeostasis, we evaluated whether specific isoenzymes were involved in this event. To address this question, Western blotting analysis was performed on both sub- and post-confluent ROS.SMER #14 cells using antibodies against different PKC isoforms. In conclusion, our preliminary data indicate that estrogen responsiveness of osteoblastic cells can be highly regulated by PKC. Finally, these data suggest that this intracellular interaction might play an important role in modulating hormonal and pharmacological responsiveness of bone tissue.
Steroids
PMID:Protein kinase C modulates estrogen receptors in differentiated osteoblastic cells in vitro. 961 1

The present study used in situ hybridization histochemistry to compare the distribution of estrogen receptor (ER)-alpha and ER-beta mRNA-containing cells in rat pituitary, gonads, uterus, and prostate of intact animals or after hormonal manipulations. Cryostat tissue sections were hybridized with 35S-labeled antisense riboprobes complimentary to ER-alpha or ER-beta mRNA, stringently washed and apposed to emulsion. The results of these studies indicate that the expression of the two receptors is tissue and region specific, with estrogen target tissues specifically expressing ER-alpha, ER-beta, or both forms of ER. In the intact rat, ER-alpha and ER-beta mRNA were both seen in the pituitary, although more cells expressed ER-alpha than ER-beta mRNA. The distribution of the two transcripts in the ovary was qualitatively different, with ER-alpha being primarily localized in the stromal cells, while ER-beta mRNA was concentrated in the granulosa cells of developing follicles. In the uterus, ER-alpha mRNA was abundant in the stromal and epithelial cells of the endometrium, while only very weak ER-beta hybridization signal was detected in these cells. ER-beta mRNA-expressing cells, but not ER-alpha, were also detected in the prostate and in the Sertoli cells, and the large, round spermatocytes of the testis. Gonadectomy markedly attenuated the expression of ER-beta mRNA in the peripheral tissues, with the level of ER-beta mRNA in the uterus and prostate reduced to non-detectable levels. The results of these in situ hybridization studies demonstrate that the distribution and regulation of ER-beta mRNA expression is tissue specific and different from ER-alpha mRNA. The differential expression of ERs in these tissues may explain in part the tissue selective activity of estrogenic compounds.
Steroids 1998 Oct
PMID:Comparative distribution of estrogen receptor-alpha (ER-alpha) and beta (ER-beta) mRNA in the rat pituitary, gonad, and reproductive tract. 980 Feb 79

Estradiol-17beta (E2) can inhibit vascular smooth muscle cell (VSMC) proliferation probably through its ability to activate its nuclear estrogen receptors (ER). Activation or inhibition of the ER by cognate permissive or non-permissive ligands, respectively, would indicate whether ER action is critical for this vascular protective effect. We investigated a previously characterized population of cultured porcine coronary artery SMCs for ER expression and for the response of these cells to estrogens and antiestrogens. Reverse transcription-polymerase chain reaction and Western blot analyses demonstrated ER mRNA and protein, respectively, in these cells. While the culture conditions required may have prevented the demonstration of physiological effects of E2, the antiestrogens, ICI 182,780 and 4-hydroxytamoxifen, stimulated VSMC proliferation. The data suggest that, by interrupting ER function, antiestrogens significantly increased the VSMC mitotic rate. This model may be used to identify ER-regulated genes that function to control the growth of these coronary artery SMCs.
Steroids 1999 Jul
PMID:Inhibition of estrogen receptor function promotes porcine coronary artery smooth muscle cell proliferation. 1044 3

Estrogens and selective estrogen receptor modulators are used for the treatment and prevention of conditions resulting from menopause. Since estrogens exert their activity by binding to nuclear receptors, there is intense interest in developing new ligands for the two known estrogen receptor subtypes, ER-alpha and ER-beta. Characterization assays used to profile new estrogen receptor ligands often utilize receptors from different species, with the assumption that they behave identically. To test this belief, we have profiled a number of estrogens, other steroids, phytoestrogens and selective estrogen receptor modulators in a solid phase radioligand binding assay using recombinant protein for human, rat, and mouse ER-alpha and ER-beta. Certain compounds show species dependent binding preferences for ER-alpha or ER-beta, leading to differences in receptor subtype selectivity. The amino acids identified by crystallography as lining the ligand binding cavity are the same among the three species, suggesting that as yet unidentified amino acids contribute to the structure of the binding site. We conclude from this analysis that the ability of a compound to selectively bind to a particular ER subtype can be species dependent.
Steroids 2002 Apr
PMID:The ligand binding profiles of estrogen receptors alpha and beta are species dependent. 1195 94

Tibolone is a synthetic steroid that is prescribed to postmenopausal women for relief of climacteric symptoms and prevention of osteoporosis. It has been reported to be metabolized in a tissue-selective manner to three steroids that collectively have weak estrogenic, progestogenic, and androgenic activities. Recently, a new tibolone metabolite, 7alpha-methyl-17alpha-ethynyl-17beta-estradiol (7alpha-Me-EE2), was identified in women. In this report, we describe the pre-clinical estrogenic activities of this metabolite and compare these effects to those obtained with 17alpha-ethynyl-17beta-estradiol (EE2) and 17beta-estradiol (E2). In an in vitro ligand-binding assay, 7alpha-Me-EE2 bound to both human estrogen receptor (ER)-alpha and -beta with IC(50)'s of 1.2 and 3.0 nM, respectively. Using MCF-7 human breast cancer cells that express high levels of ER-alpha, 7alpha-Me-EE2 transactivated an estrogen response element (ERE)-tk-luciferase reporter gene construct with an EC(50) of 0.021 nM. Likewise, 7alpha-Me-EE2 stimulated MCF-7 breast cancer cell proliferation with an EC(50) of 0.002 nM. In immature female rats, subcutaneous (s.c.) administration of 7alpha-Me-EE2 stimulated uterine wet weight gain with an ED(50) of 0.2 microg/kg. Moreover, 7alpha-Me-EE2 induced uterine complement component C3 gene expression, an estrogenic marker of epithelial cell stimulation, with an ED(50) of 0.5 microg/kg. When compared to EE2 and E2, 7alpha-Me-EE2 exhibited equivalent or greater potencies and efficacies in these assays. In summary, these results indicate that 7alpha-Me-EE2 is a very potent estrogen. This steroid appears to be the most potent estrogenic metabolite of tibolone identified to date, and additional studies are, therefore, warranted regarding the role of this metabolite in the biological actions of the drug.
Steroids 2002 Jul
PMID:Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolite. 1211 14


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