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Results for “Hormone Receptors--analysis”

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PubMed1988

Influence of mastectomy technique on sex steroid receptor analysis.

Accurate analysis of hormone receptors in breast carcinoma is critical from prognostic and therapeutic standpoints. Controversy exists over whether there is receptor decay when specimens are obtained upon completion of, rather than prior to, mastectomy. In addition, the effect of mastectomy technique on receptor concentration has not been addressed. Twenty patients with breast carcinoma had biopsy specimens taken prior to and upon completion of modified radical mastectomy. Ten had axillary dissection followed by mastectomy (Group A). The others had mobilization of the breast before axillary dissection (Group B). The estrogen receptor concentration was higher in 14 of 20 premastectomy specimens. All 10 patients in Group B had positive receptors before mastectomy; 5 were negative after mastectomy. All seven patients in Group A with positive premastectomy receptors remained so postmastectomy. We concluded that if a tumor specimen for receptor analysis is not obtained prior to modified radical mastectomy, axillary dissection should precede breast mobilization.

Axilla↗

PubMed1991

The biology of beta-adrenergic receptors: analysis in human epidermoid carcinoma A431 cells.

1. G-protein-linked transmembrane signaling has emerged as a major pathway for information transduction across the cell membrane. 2. In addition to photopigments that propagate the signal from light, cell-surface receptors for hormones, neurotransmitters, and autacoids propagate signals from ligand binding to membrane-bound effector units via G-proteins. 3. Biochemical and molecular features of one prominent member of these receptors, the beta-adrenergic receptor, will be highlighted in the present article. 4. The role of the human epidermoid carcinoma A431 cells as a model for the study of the structure and biology of beta-adrenergic receptors will be emphasized. 5. A model for receptor regulation, gleaned from recent advances in the biochemistry, cell and molecular biology of beta-adrenergic receptors, is discussed.

Amino Acid Sequence↗

PubMed1985

Comparison of histo- and biochemical methods for estrogen and progesterone receptor analysis in primary human breast carcinoma.

One hundred and twenty-three primary breast carcinomas have been examined under optimal procedural conditions for presence and quantity of estrogen (ER) and progesterone (PgR) receptors by a histochemical method using hormones conjugated to fluoresceinated bovine serum albumin and by a conventional biochemical (dextran-coated charcoal) assay. The semiquantitative histochemical results for ER and PgR were strongly positively correlated, as were the corresponding quantitative biochemical results, but there was no significant correlation between histo- and biochemical results for ER, nor between the corresponding results for PgR. By generally accepted cut-off limits for positivity there was an equal frequency of ER- and PgR-positive tumors by the histochemical method (71 and 67% respectively), whereas there was a significantly higher frequency of ER- than PgR-positive tumors by the biochemical method (76 and 59%). The qualitative agreement between the two methods was 76% for ER and 61% for PgR, and there was a correspondingly inferior sensitivity and specificity of the histochemical method in comparison with the biochemical method, whose value is clinically validated.

Breast Neoplasms↗

PubMed1987

Progesterone receptor activity and the response to the first endocrine therapy in advanced breast cancer.

The predictive value of the progesterone receptor activity (PgR) was studied in a group of 84 patients with estradiol receptor (ER) positive advanced breast cancer who received their first endocrine treatment (tamoxifen or ovariectomy), with special emphasis on the timing of the receptor analysis. All patients were treated at 1 center and receptor analyses performed in 1 laboratory. In the group of 27 patients with PgR analysis performed immediately prior to the start of treatment, 14 out of 18 PgR+ve and only 2 out of 9 PgR-ve patients responded (P less than 0.02). In contrast, when PgR was analysed greater than 6 months prior to the start of treatment, the response rates for PgR+ve and PgR-ve patients did not differ significantly: 55% vs. 33% respectively. With regard to quantitative rather than qualitative PgR data, PgR levels exceeding 100 fmol/mg protein irrespective of ER levels, are an excellent indicator of hormonal responsiveness with a response rate of more than 80%, even if PgR analyses are performed long before the start of treatment.

Breast Neoplasms↗

PubMed1990

[Long-term study of the significance of hormone receptors as prognostic factors in breast cancer].

To check the question as to the prognostic significance of oestrogen and progesterone receptors in invasive breast cancer, the course of the disease was registered in 660 patients in the context of a retrospective study. These patients had been operated on with the objective of curing breast cancer between 1976 and 1984. A receptor analysis of these patients is available with regard to both receptor types. Positive progesterone receptors could be detected in 38%, positive oestrogen receptors in 70%. Values over 15 fmol/mg tissue protein were rated as positive. The proportion of oestrogen-receptor-positive tumours increased with the age of the patients. On the other hand, the progesterone receptor did not show this dependence. During analysis of the median receptor concentrations as well as of the progesterone combinations, a correlation between the axillary lymph node status and the hormone receptor status of the primary tumour could not be observed for the two receptor types. The survival time in relation to the oestrogen receptor status did not indicate any significant effect on survival time. On the other hand, the improvement of survival time depending on the positive progesterone receptor status was highly significant in statistical terms (p less than 0.001) especially in nodal-positive patients. Both patients with axillary lymph node metastases and positive progesterone status, compared with patients without lymph node invasion and a negative progesterone status, had the same survival rate.

Adult↗

PubMed1991

Regulatory functions of a non-ligand-binding thyroid hormone receptor isoform.

Gene regulation by thyroid hormones is mediated through multiple nuclear receptors. Only some of these thyroid hormone receptor (TR) isoforms become transcriptional enhancers in the presence of the thyroid hormone T3. Here we analyze the regulatory function of the human TR alpha 2 isoform. This protein does not bind T3 and is not a transcriptional activator of thyroid hormone-responsive elements (TRE). Transfected TR alpha 2 functions as a constitutive repressor of the transcriptional activators TR alpha 1 and TR beta 1 but also represses heterologous receptors, including the retinoic acid receptor and the estrogen receptor, which can activate TRE-controlled genes. TR alpha 2 protein showed strongly reduced DNA binding to a palindromic TRE when compared with the active TRs. Hybrid receptor analysis revealed that the special properties of the TR alpha 2 protein, including its repressor function and DNA binding characteristics, are intrinsic properties of its carboxyterminus and can be transferred to other receptors. Although it has been shown that the active TRs can act as repressors and silencers due to their strong DNA binding in the absence of hormone, our data show that TR alpha 2 is unlikely to inhibit TRs and other receptors through a competitive DNA binding mechanism. Antibody gel shift experiments suggest that repression by TR alpha 2 might result from interaction with active receptors. Thus, the receptor-like TR alpha 2 isoform differs from typical nuclear receptors in its DNA-binding and ligand-binding properties and appears to regulate the activity of other receptors via protein-protein interaction.

Base Sequence↗

PubMed1981

Polypeptide-binding membrane receptors: analysis and classification.

Polypeptide receptors on mammalian plasma membranes can be categorized on the basis of function. The binding of ligand by class I receptors results in changes in cell metabolism or behavior. Hormone-receptor interactions typify this group. The binding of ligand by class II receptors in ligand internalization. Although changes in cellular activity may result from metabolism of the internalized ligand, the interaction between ligand and class II receptor does not itself lead to alterations in cell behavior. Class II receptors include those for low-density lipoproteins and for alpha-macroglobulin-protease complexes. Although receptors within each category are chemically disparate, they show striking similarities in behavior. Analysis of the behavioral patterns of receptors in each category reveals insights into receptor physiology and allows for a prospective analysis of receptor characteristics.

Animals↗

PubMed1992

Effects of thyroid hormone on myocardial adrenergic beta-receptor responsiveness and function during late gestation.

To assess the effect of fetal hypothyroidism during late gestation on postnatal cardiovascular responsiveness, we measured heart rate and cardiac output responses to isoproterenol in newborn lambs. To evaluate the effect of such altered thyroid status on the development of beta-adrenergic signaling cascade, we measured myocardial beta-adrenergic receptor concentration and affinity, guanine nucleotide regulatory protein density, and adenylyl cyclase responsiveness. Twenty fetal lambs underwent either thyroidectomy and line placement or line placement alone at 128-130 d gestation. Five thyroidectomized and six control newborns were treated with isoproterenol, five thyroidectomized and four control newborns were killed upon delivery and tissue was obtained for biochemical studies, and four additional animals were delivered and killed at 126 d gestation and tissue was obtained for receptor analysis. Of the newborns treated with isoproterenol, the thyroidectomized lambs showed lower increase in heart rate and cardiac output compared with euthyroid newborns. Compared with the myocardium of normal newborns of similar gestation, the myocardium of the newborns who underwent fetal thyroidectomy failed to show the normal increase in beta-adrenoceptors accompanied by reduction in beta-adrenergic-stimulated adenylate cyclase activity. These results suggest that near term, the normal development of ovine fetus myocardial beta-adrenergic receptor is affected by thyroid hormones.

Adenylyl Cyclases↗

PubMed1985

Pancreatic hormone receptors on islet cells.

To assess whether islet cells are equipped with recognition units which allow an intra-islet regulation via released hormones, the presence of insulin and glucagon receptors is investigated on purified pancreatic A and B cells. Mono-[125I]glucagon is shown to bind specifically to islet B cells, with similar binding characteristics as in isolated hepatocytes but involving less receptors per cell (2.10(4) per B cell vs. 8.10(5) per liver cell). Binding is half-maximally displaced by 5.10(-9) M glucagon, a concentration known to induce half-maximal biological effects in isolated B cells. These results are compatible with a regulatory role of glucagon in the insulin release process. No specific binding of [125I]tyr-A14-insulin is detected on pancreatic A cells. In order to increase receptor assay sensitivity, [123I]tyr-A14-insulin is prepared with at least 5-fold higher specific activity. Its validity for in vitro receptor analysis is demonstrated in IM-9 lymphocytes, where insulin binding is detectable down to 10(4) cells/ml. However, no insulin-binding sites are identified on pancreatic A cells, even at 10(6) cells/ml. If isolated A cells contain high affinity insulin receptors, their number should be inferior to 400 per cell, which is 50- to 500-fold lower than in classical insulin target cells. These findings explain the insensitivity of the glucagon release process to acute exposure to insulin.

Animals↗

PubMed1992

Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts.

The ligand specificity and biochemical properties of the human (h) FSH receptor are poorly characterized due to the low abundance of these receptors and the limited availability of human tissues. Using a fragment of rat FSH receptor cDNA, we screened a human testicular cDNA library and obtained a FSH receptor cDNA covering the entire amino acid-coding region. After transfection of a human fetal kidney cell line (293) with the hFSH receptor cDNA, radioligand receptor analysis revealed the presence of high affinity (Kd, 1.7 x 10(-9) M) FSH-binding sites on the plasma membrane. Both recombinant and wild-type hFSH displaced [125I]hFSH binding, with ED50 values of 25 and 70 ng/ml, respectively, whereas hLH, hCG, and hTSH were ineffective. Although human, rat(r), and ovine FSH as well as equine CG competed for rat testicular FSH receptor binding, only hFSH and rFSH interacted effectively with the recombinant hFSH receptor, suggesting that species-specific ligand recognition exists between human and rodent receptors. After incubation of transfected cells with hFSH, but not recombinant hLH or hCG, a dose-dependent increase (ED50, 10 ng/ml) in extracellular cAMP accumulation was observed, indicating a functional coupling of the expressed human receptor with the endogenous adenyl cyclase. In cells cotransfected with the FSH receptor expression plasmid and a luciferase reporter gene driven by the promoter of a cAMP-responsive gene, treatment with hFSH, but not hCG, resulted in a dose-dependent increase in luciferase activity. Northern blot analysis using a cRNA probe derived from the human receptor cDNA indicated the presence of multiple FSH receptor mRNA transcripts (7.0, 4.2, and 2.5 kilobases) in RNA prepared from human follicular phase ovary, but not from human corpus luteum or placenta. Additionally, two FSH-binding sites of 76 and 112 kilodaltons were detected in transfected 293 cells after ligand/receptor cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. These results demonstrate the expression of functional hFSH receptor with unique ligand specificity and provide new data on the biochemical properties of the human receptor at the mRNA and protein levels.

Animals↗

PubMed1992

Characterization of angiotensin-II receptor subtype on bovine thecal cells and its regulation by luteinizing hormone.

In this study the primary objectives were to localize angiotensin-II (AII) receptors on specific ovarian cells and determine whether these receptors are regulated by LH. AII receptor analysis, carried out using membrane fractions prepared from isolated thecal, granulosa, and luteal cells from bovine ovary, revealed that [125I]AII-binding sites were present only on thecal cells. The Kd and binding capacity were determined to be 0.29 +/- 0.08 nM and 66.9 +/- 8.1 fmol/mg membrane protein (mean +/- SEM from three experiments, each with duplicate determinations), respectively. None of the peptides unrelated to AII affected the binding of [125I]AII. Unlabeled AII, saralasin, and AIII were equipotent (IC50, approximately 5 nM for all three peptides) in competing with the radioligand. However, the binding affinity for AI was less by almost 2 log units. Using AII receptor subtype-specific nonpeptide antagonists, Losartan [a selective antagonist for the type 1 AII (AT1) receptor] and PD 123319 [a selective antagonist for the type 2 AII (AT2) receptor], AII receptors on thecal cells could be classified pharmacologically as AT2-type receptors. The IC50 determined from the competitive binding inhibition experiments for the various unlabeled competing substances were 5 nM, 20 nM, 200 nM, and 200 microM with respect to AII, p-amino-phenylalanine-AII, PD123319, and Losartan, respectively. Thecal cells cultured in a serum-free medium also expressed AII receptors, which could be up-regulated by LH or 8-bromo-cAMP in a dose-dependent manner. The number of AII receptors on thecal cells nearly doubled when the cells were cultured in the presence of 100 ng/ml LH, with little change in their Kd value. This increase in the number of AII receptors was inhibitable by a protein synthesis inhibitor, cycloheximide. In summary, we have demonstrated that in the bovine ovary, AII receptors belonging to AT2 subclass are predominantly expressed on thecal cells, and these receptors can be up-regulated by LH via a cAMP-dependent mechanism. Thus, the bovine thecal cells in primary culture can potentially become a useful in vitro system to study the mechanism of regulation of AII receptor induction as well as the so far unknown function of this class of receptor.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Design and synthesis of a novel biotinylated photoreactive insulin for receptor analysis.

B1-(4-Azido-salicyloyl)-[B1-biocytin,B2-lysine]insulin was synthesized by double Edman degradation of A1,B29-Msc2-insulin and stepwise acylation at the N-terminus of the B-chain. This derivative is homogeneous in RP-HPLC and has a biological in vitro activity of 20% and receptor binding of 15%, relative to insulin. Radioiodination and HPLC gave the B1-labelled 125I-derivative (I) as well as the 4 isomers with 125I-labelled tyrosine (A14, A19, B16, B26). UV-induced crosslinking of I with insulin receptors led to specific labelling of the alpha-subunit (Mr 130,000). The peptide bond LysB2-AspB3 is completely cleavable by trypsin (EC 3.4.21.4). I is thus a new tool for the analysis of the hormone-binding region by making possible the isolation of tryptic, biotinylated receptor fragments labelled by the dipeptide 125I-4-azidosalicyloyl-biocytinyl-Lys.

Affinity Labels↗

PubMed1989

A monoclonal antibody to lactogenic receptors from female rat liver.

Affinity-purified lactogenic receptors from female rat liver microsomal membranes were used to raise antibodies in female Balb/c mice. Mouse spleen and myeloma cells were fused and hybridoma-derived monoclonal antibodies (Mabs) were produced by in-vitro cell culture. Mab from a selected clone was sequentially purified by chromatography on a thiophilic gel and on agarose-bound protein A. The Mab was found to be of IgG1 subclass and of kappa type. The Mab recognized membrane-bound and solubilized (by the detergent heptaoxyethylene lauryl ether; G3707) receptors as well as receptors purified by affinity chromatography and subsequent sodium dodecyl sulphate (SDS) electrophoresis from female rat liver. The Mab bound to receptors from several other female rat tissues, such as ovary, kidney and adrenal, whereas there was no binding to liver receptors from cow and rabbit. Displacement experiments showed that the Mab was specific for a lactogenic type of receptor, in agreement with the finding that the Mab did not recognize receptors from male rat liver. The Mab also bound to cytoplasmic receptors (present in the supernatant after centrifugation at 100,000 g) from female rat liver, suggesting a structural similarity between the cytoplasmic and the microsomal receptors. Analysis of purified receptors by SDS electrophoresis and subsequent Western blot with 125I-labelled Mab as a probe showed one band corresponding to an Mr of 45,500 +/- 2500 (n = 5). The same band was obtained with 125I-labelled human GH, showing that the Mab binds to the unit which accommodates the hormone-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

LH-RH receptors in the human pancreas. Basis for antihormonal treatment in ductal carcinoma of the pancreas.

LH-RH-, estrogen-, and progesterone-receptor binding was measured in the human pancreas of patients with ductal pancreatic cancer (n = 23) and chronic pancreatitis (n = 15), and of organ donors (n = 11). Receptor analysis was determined by incubation of the homogenized tissues with estrogen, progesterone, and the LH-RH analog buserelin labeled with iodine-125. Only one biopsy (9%) from normal pancreas had an LH-RH-receptor concentration greater than 3 fmol/mg membrane protein. LH-RH binding levels greater than 3 fmol/mg were detected in 67% of patients with chronic pancreatitis and in 57% of patients with pancreatic cancer. Progesterone levels greater than 15 fmol/mg membrane protein were found in 36% of normal pancreas, in 27% of chronic pancreatitis, and in 17% of pancreatic cancer cases, respectively. The highest concentration of estrogen receptors (greater than 15 fmol/mg membrane protein) was seen in normal pancreas (73%). The increase in LH-RH-receptor concentration in chronic pancreatitis and pancreatic cancer seems to be unspecific, but might be of benefit for antiproliferative treatment in pancreatic cancer.

Adult↗

PubMed1990

[Endometrial cancer and steroid hormone receptors].

Endometrial carcinoma, now the most frequent female genital tract malignancy in Denmark, is generally accepted as an endocrine-related neoplasm. Like normal endometrium, many endometrial carcinomas contain estrogen receptors as well as progesterone receptors. The receptor content appears to correlate with several histopathological features, in particular with tumour differentiation. Well-differentiated lesions are more frequently estrogen and progesterone receptor "positive" than poorly differentiated lesions. Several studies suggest that a high content of estrogen/progesterone receptors in primary endometrial carcinomas, regardless of other prognostic factors, affects the prognosis favourably. Furthermore, receptor status seems to correlate with response of the tumour to progestin therapy. It may be of particular importance, that nearly half of poorly differentiated endometrial carcinomas contain estrogen/progesterone receptors and thus might benefit from progestin therapy. Immunohistochemical receptor analysis directly on cryostat or formalin-fixed tissue sections increases the possibility to explore the histological and biological features, which are determinative for the receptor profile of endometrial carcinomas.

Carcinoma↗

PubMed1978

Estradiol receptor analysis in human breast cancer tissue by isoelectric focusing in polyacrylamide gel.

Isoelectric focusing in polyacrylamide gel combined with limited proteolysis is a simple and specific method for quantitation of estradiol receptors in breast cancer tissue. At least eight different samples can be analyzed simultaneously on one gel, and the whole procedure, including sample preparation, takes less than 7 hr. In comparison with sucrose gradient centrifugation, isoelectric focusing is more sensitive, possibly due to the short time (1.5 to 2 hr) needed for the analysis. Furthermore, only one incubation with tritium-labeled estradiol is needed for an analysis, which means that a smaller amount of tumor tissue is needed than for most other methods. This fact allows analysis of the estrogen receptor content in tumor material obtained from fine-needle biopsy.

Breast Neoplasms↗

PubMed1975

The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor.

NSILA-s (nonsuppressible insulin-like activity, soluble in acid ethanol) is a serum peptide that has insulin-like and growth-promoting activities. We have demonstrated previously that liver plasma membranes possess separate receptors for NSILA-s and insulin and have characterized the insulin receptor in detail. In the present study we have characterized the properties and specificity of the NSILA-s receptor and compared them to those of the insulin receptor in the same tissue. Both 125I-NSILA-s and 125I-insulin bind rapidly and reversibly to their receptors in liver membranes; maximal NSILA-s binding occurs at 20 degrees while maximal insulin binding is seen at 1-4 degrees. The pH optimum for NSILA-s binding is broad (6.0 to 8.0), in contrast to the very sharp pH optimum (7.5 to 8.0) for insulin binding. Both receptors exhibit a high degree of specificity. With the insulin receptor, NSILA-s and insulin analogues compete for binding in proportion to their insulin-like potency: insulin greater than proinsulin greater than NSILA-s. With the NSILA-s receptor, NSILA-s is most potent and the order is reversed: NSILA-s greater than proinsulin greater than insulin. Furthermore, six preparations of NSILA-s which varied 70-fold in biological activity competed for 125I-NSILA-s binding in order of their potencies. NSILA-s which had been inactivated biologically by reduction and aminoethylation and growth hormone were less than 1/100,000 as potent as the most purified NSILA-s preparation. Purified preparations of fibroblast growth factor, epidermal growth factor, nerve growth factor, and somatomedins B and C were less than 1% as effective as NSILA-s in competing for the 125I-NSILA-s suggesting that these factors act through other receptors. In contrast, somatomedin A was 10% as active as NSILA-s and multiplication-stimulating activity was fully as active as NSILA-s in competing for the NSILA-s receptor. Analysis of the data suggests that there are approximately 50 times more insulin receptors than NSILA-s receptors per liver cell, while the apparent affinity of NSILA-s receptors is somewhat higher than that of the insulin receptor.

Animals↗

PubMed1985

[Hormonal therapy of endometrial cancer].

Progestin therapy is indicated for advanced or metastatic endometrial cancer as well as a adjuvant therapy for primary cancer. There are several predictors of tumor responsiveness to the hormone. Sex steroid receptor(R) is a biochemical marker. Receptor analysis was done in 73 cases of primary endometrial cancer. The concentrations of estrogen (E), progestin (P) and androgen (A) were found to correlate with the degree of tumor differentiation; well-differentiated tumor contains significantly greater receptors than moderately-and poorly-differentiated tumors. Both ER and PR were positive in about 80% of the well-differentiated tumor, but negative in 50% of the poorly-differentiated tumors. Analysis of 13 cases of death shows some correlation of the PR concentrations with the survival time. Receptor dynamics in tumor of the patients enables us to predict possible site(s) of impaired responsiveness to progestin. Furthermore, in addition to progestin and estrogen test, tamoxifen challenge test is useful as in vivo sensitivity test. Moreover, receptor manipulation by tamoxifen may be employed to enhance hormonal sensitivity of the tumor, particularly the low receptor one.

Female↗