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Results for “Hormone Receptors--analysis”

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PubMed1978

Correlation between clinical response to hormone therapy and steroid receptor content in prostatic cancer.

Hormonal therapy is the dominating form of treatment for prostatic carcinoma. The majority of cases (80%) are well controlled for varying times with this regimen. However, thus far there have been no adequate methods to predict in which cases hormonal therapy is of less benefit. Measurement of cancer tissue content of intracellular hormone receptors constitutes progress toward a more individualized therapy in prostatic carcinoma. In this study biopsies from 16 cancer patients were taken before therapy was given, and the specimens were analyzed with regard to content of specific methyltrienolone-binding sites. A correlation has been made between receptor content and clinical response to hormonal therapy in each case. Twelve specimens contained measurable amounts of steroid receptors. Of these, one patient died during irradiation therapy before onset of hormonal treatment. However, of the remaining 11 patients, 9 responded well to hormones (9/11 approximately 82%). The two receptor-positive nonresponders had the lowest measurable receptor levels in the series. Four specimens contained no detectable amounts of receptors. Three of these patients showed no response to therapy (3/4 = 75%) but one was "false negative." Our data indicate that steroid receptor analysis may become a valuable diagnostic tool in individualizing the therapy for prostatic cancer.

Aged↗

PubMed1979

Steroid receptor content in human prostatic carcinoma and response to endocrine therapy.

Biopsy material from primary prostatic carcinoma from 25 patients was analyzed with regard to cytosol content of methyltrienolone (a synthetic androgen) binding sites and the receptor content has been correlated to the clinical response to endocrine therapy. A dextran-coated charcoal technique was used and binding data were calculated from Scatchard plots. In 20 of the tumors detectable levels of methyltrienolone receptor were noted. One of the receptor-positive patients died during radiation therapy before onset of hormonal treatment, and a second patient, who had a highly differentiated carcinoma, so far has not received any endocrine therapy. Of the remaining 18 patients 15 responded well to castration, treatment with estrogens, or Estracyt (approximately 80%). The biopsies from two of the three receptor-positive non-responders contained the lowest measurable receptor levels. Five specimens lacked detectable amounts of methyltrienolone receptor. Four of these patients did not respond to therapy (approximately 80%), but one was "false" negative. Our data indicate that steroid receptor analysis may become an important tool in predicting the value of endocrine therapy in human prostatic carcinoma.

Aged↗

PubMed1990

[Steroid receptors and atypical histology as prognostic parameters in meningioma].

Cytosolic oestrogen and progesterone receptors (ER and PR) were determined in 58 primary and 13 recurrent meningiomas and related to their histological and clinical features. ER levels were low or not detectable (range 0-34 fmol/mg prot., median 0 fmol), whereas considerable amounts of PR were found in 69% of primary tumours (range 0-583 fmol/mg prot., median 72 fmol) and in 5/5 long-term recurrences (range 69-505 fmol/mg prot., median 143). Eight tumours recurred within a short-term period (less than 5 years) with a low PR expression (range 0-34 fmol/mg prot., median 0 fmol) and all presented raised cellularity and mitotic rate ("atypical" meningioma) or criteria of definitely malignant meningioma. The primary tumours of the short-term recurrences were not available for receptor analysis; however, they also were either "atypical" or anaplastic meningiomas. Long-term recurrences never displayed other than classical histology. From our results we conclude that polymorphy, as well as a lack of PR are strong indicators for short-term recurrence.

Brain↗

PubMed1990

Male breast cancer--a 20-year review of 16 cases at Yonsei University.

Sixteen cases of male breast cancer seen over a 20-year period were reviewed. The causes of cancer of the male breast are no better understood, but major alterations in hormonal environment could be a significant factor. Some clinical characteristics correspond well with the results of other series. The median age at presentation was 61.7 years. The most frequent initial symptom was a painless mass, and the incidences of nipple discharge, central tumor location, and axillary node involvement were high. Males also had a higher incidence of local advancement which was associated with a longer delay in seeking treatment and small breast tissue. The pathologic type was infiltrating ductal type in all cases except one, and all cases showed favorable nuclear grade. Estrogen receptor analysis was performed from the tumor of 2 patients. Both of them showed a high receptor level. There was no locoregional relapse in 5 patients who received adjuvant radiotherapy in contrast to the 2 relapses in 3 patients who underwent surgery alone. And three of the five patients who received radiotherapy suffered from systemic metastasis which suggested the important role of adjuvant chemotherapy as well as radiotherapy. In light of the encouraging results about adjuvant chemotherapy in the treatment for female breast cancer with axillary lymph node involvement, it would be desirable to extend this policy to male breast cancer.

Adenocarcinoma↗

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↗

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↗

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↗