Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of magnal estrogen and progesterone receptors during egg formation in the hen were determined. Hens were sacrificed at various times after ovulation and magnal receptor levels were determined by tritiated hormone binding assays. A coincident increase in nuclear estrogen receptor and decrease in cytosol estrogen receptor 2 to 4 h postoviposition was suggestive of in vivo receptor translocation. At 12 to 16 h postoviposition cytosol progesterone receptor increased 2-fold and subsequently declined during the time of preovulatory progesterone surge (8 h to 6 h prior to expected ovulation). These data suggest that changes in circulating levels of estrogen and progesterone, associated with ovulation, are coordinated with oviductal function. This is reflected by fluxes of their respective oviductal receptors.
Steroids 1984 Mar
PMID:Magnal steroid hormone receptors during egg formation in the domestic hen. 652 43

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

Functional rat estrogen receptor beta ligand binding domain (rER beta LBD, aa 210-485) and human estrogen receptor alpha ligand binding domain (hER alpha LBD, aa 301-553) were expressed in Escherichia coli. Hormone binding assays revealed that both ER beta and ER alpha LBDs bound the natural ligand estradiol (E2) with similar affinity (Kd approximately 100 pM). Competitive binding experiments were carried out with ICI 164384, 4-hydroxytamoxifen, 16 alpha-bromo-estradiol, and genistein employing [3H]E2 as a tracer. No significant differences in responses of ER alpha and ER beta LBDs to ICI 164384 and 4-hydroxytamoxifen were observed, 16 alpha-Bromo-estradiol and genistein discriminated between the ER subtypes and acted as ER alpha and ER beta selective ligands, respectively. Final purification of recombinant proteins was achieved on an E2 affinity column, where they were subjected to in situ carboxymethylation. The partially carboxymethylated proteins actively bound E2. The carboxymethylated rER beta LBD had a molecular mass of 32251.6 Da, equivalent to the calculated mass with the addition of three carboxymethyl groups. No other proteins (of lower or higher molecular mass) were detected, so the LBD was considered structurally authentic and pure. By using a combination of intact protein mass spectrometric fragmentation and trypsin proteolysis (98% sequence coverage), it was established that rER beta cysteine-289 and -354 were not carboxymethylated on the affinity column, suggesting that they were shielded from alkylation in the E2-bound conformational state. Concurrent analysis of hER alpha LBD showed that under the same experimental conditions, the two equivalent ER alpha cysteines were not alkylated (alpha C381 and alpha C447). These data support close structural relationship between the E2-bound ER alpha LBD and ER beta LBD proteins.
Steroids
PMID:Characterization of bacterially expressed rat estrogen receptor beta ligand binding domain by mass spectrometry: structural comparison with estrogen receptor alpha. 929 36

Estrogen is of vital importance for the development and control of reproductive functions. Until recently, estrogen was believed to regulate complex programs of gene expression by binding to an unique nuclear receptor belonging to the superfamily of ligand-dependent transcription factors. However, the identification of a second estrogen receptor, referred to as ER beta, is leading to a re-evaluation of estrogen signaling and physiology.
Steroids
PMID:Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling. 961 97

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

Steroids act on the follicle through autocrine and paracrine mechanisms to regulate follicular growth and steroidogenesis. Estradiol plays a significant role in determining the fate of the developing follicle and acts via specific receptors which are nuclear transcription factors. It has been established that besides classical estrogen receptor-alpha (ER alpha) novel forms termed ER beta exist. In species studied to date these two types of ERs exhibit different tissue localisation patterns and levels of expression. The present study was performed to determine whether ER alpha and ER beta are differentially expressed in the porcine ovary. Immunohistochemical studies using antibodies to ER alpha and ER beta, established the predominance of ER beta over ER alpha in the porcine ovary. Cyclical changes in estrogen receptor-beta expression were observed. The immunostaining was present in all types of follicles, and decreased in corpus luteum while it regressed. In the contrary estrogen receptor-alpha staining was seen only in large preovulatory follicle and in early corpora lutea.
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PMID:Differential distribution of estrogen receptor-beta and estrogen receptor-alpha in the porcine ovary. 1145 37

The plasma membrane form of the estrogen receptor-alpha (mER-alpha) is involved in rapid estrogen-induced prolactin release from GH(3)/B6 rat pituitary tumor cells and can be detected immunocytochemically using several estrogen receptor-alpha (ER-alpha) antibodies. We recently described staining of fixed cells via a biotin-avidin-alkaline phosphatase sandwich assay. From this protocol, we have developed a rapid, quantifiable 96-well plate immunoassay for mER-alpha, using a different alkaline phosphatase substrate, para-nitrophenylphosphate, which generates a soluble yellow product, para-nitrophenol. We also permeabilized cells with detergent during fixation to measure intracellular ER-alpha (iER-alpha) with the same assay and then compared intracellular versus membrane ER-alpha levels in two GH(3)/B6 cell subclones originally selected for high and absent mER-alpha expression by immunocytochemistry. While the F10 subclone expresses plentiful amounts of the mER-alpha, the D9 subclone has undetectable levels of mER-alpha using this assay. In addition, there is a seven-fold difference in iER-alpha expression between the high (F10) and no (D9) mER-alpha expressing subclones. In the high mER-alpha expressing cell line, the mER-alpha totals approximately one third of total cellular ER-alpha. Neither membrane or intracellular forms of ER-beta were detected with this assay. The pNp assay allows convenient and quantitative comparison of multiple parameters of mER-alpha and iER-alpha regulation and should be applicable to other antigens that are expressed on the cell surface as well as intracellularly.
Steroids 2001 Oct
PMID:A comparison of membrane vs. intracellular estrogen receptor-alpha in GH(3)/B6 pituitary tumor cells using a quantitative plate immunoassay. 1152 34

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

Two structurally related subtypes of oestrogen receptor (ER), known as alpha (ER alpha, NR3A1) and beta (ER beta, NR3A2) have been identified. ER beta mRNA and protein have been detected in a wide range of tissues including the vasculature, bone, and gonads in both males and females, as well as in cancers of the breast and prostate. In many tissues the pattern of expression of ER beta is distinct from that of ER alpha. A number of variant isoforms of the wild type beta receptor (ER beta 1), have been identified. In the human these include: (1). use of alternative start sites within the mRNA leading to translation of either a long (530 amino acids, hER beta 1L) or a truncated form (487aa hER beta 1s); (2). deletion of exons by alternative splicing; (3). formation of several isoforms (ER beta 2-beta 5) due to alternative splicing of exons encoding the carboxy terminus (F domain). We have raised monoclonal antibodies specific for hER beta1 as well as to three of the C terminal isoforms (beta2, beta 4 and beta 5). Using these antibodies we have found that ER beta 2, beta 4 and beta 5 proteins are expressed in nuclei of human tissues including the ovary, placenta, testis and vas deferens. In conclusion, in addition to the differential expression of full length ER alpha and ER beta a number of ER variant isoforms have been identified. The impact of the expression of these isoforms on cell responsiveness to oestrogens may add additional complexity to the ways in which oestrogenic ligands influence cell function.
Steroids 2002 Nov
PMID:Human oestrogen receptors: differential expression of ER alpha and beta and the identification of ER beta variants. 1239 95

Estrogenic compounds have been shown to protect neurons from a variety of toxic stimuli in vitro and in vivo and depletion of estrogen at menopause has been associated with increased risk of neurodegenerative diseases. Genistein is an isoflavone soy derivative that binds to estrogen receptors with selective estrogen receptor modulator (SERM) properties. Recent FDA recommendations of soy intake for cholesterol reduction have prompted investigation into the potentially estrogenic role of dietary soy phytochemicals in the brain. In this study, we have shown that 50nM genistein significantly reduces neuronal apoptosis in an estrogen receptor-dependent manner. The importance of apoptosis in the brain has been recognized with regard to organization of the developing brain as well as degeneration in response to disease or stroke; however, the effects of estrogenic compounds on neuronal apoptosis have not been thoroughly examined. We developed a model of apoptotic toxicity in primary cortical neurons by using the endoplasmic reticulum (ER) calcium-ATPase inhibitor, thapsigargin, to test potential anti-apoptotic effects of 17beta-estradiol and genistein. Estrogen receptor beta, but not estrogen receptor alpha, was detected in our primary neuron cultures. Thapsigargin-induced apoptosis was confirmed by loss of mitochondrial function, DNA laddering, nuclear condensation and fragmentation, and caspase activation. Both 17beta-estradiol and genistein reduced the number of apoptotic neurons and reduced the number of neurons containing active caspase-3. This effect was blocked by co-addition of ICI 182780. Our results demonstrate that genistein and 17beta-estradiol have comparable anti-apoptotic properties in primary cortical neurons and that these properties are mediated through estrogen receptors.
Steroids 2002 Dec
PMID:17beta-Estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin. 1244 Nov 88


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