Abstract:
:The interaction of tamoxifen (ICI 46,474), a synthetic antiestrogen, with uterine cytosol proteins of immature calf and rat has been studied directly using the tritiated compound labeled with a high specific activity. The binding complexes were measured by the dextrancoated charcoal, protamine sulfate and hydroxyapatite assays. Scatchard plots revealed a single class of high-affinity (KD congruent to 1.7 nM) binding sites, with a binding capacity similar to that of estradiol. Competitive experiments showed the same binding specificity for estrogens and antiestrogens. Sucrose gradient analysis revealed an 8S binding protein which could be partially proteolysed by trypsin into a 4S binding protein. Kinetic studies showed that the association rate of tamoxifen was 5 times lower than that of estradiol and reacted according to a second order kinetics. The first-order kinetics of dissociation was considerably higher than that of estradiol, giving a half-dissociation time of 20--40 min at 0--2 degrees C. In some cases tamoxifen displayed two slopes of dissociation, but the proportion of the slow-dissociating complex was always inferior to that found with estradiol. In contrast to estradiol, the kinetic constants ratio (k-/k+) gave a calculated dissociation constant, similar to that determined in equilibrium conditions (KD), agreeing with a simple reactional scheme. We conclude that the antiestrogen tamoxifen binds directly to the 8S cytosol receptor for estrogens and not to another receptor for the antagonists. In contrast to estradiol, the antagonist is rapidly dissociated from the receptor sites and is unable to protect them against thermal inactivation. The affinity of tamoxifen for its receptor sites as determined directly is surprisingly high when compared to its affinity evaluated indirectly by competitive experiments. It is then suggested that the two ligands either bind on two different sites of the same protein or induce a different conformational change of the same binding site.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Capony F,Rochefort Hdoi
10.1016/0303-7207(78)90006-0subject
Has Abstractpub_date
1978-07-01 00:00:00pages
181-98issue
2eissn
0303-7207issn
1872-8057pii
0303-7207(78)90006-0journal_volume
11pub_type
杂志文章abstract::The antiestrogen tamoxifen has been successfully used to control estrogen receptor (ER) and progesterone receptor positive breast cancer. However, the development of antiestrogen resistance is frequently observed in patients following long term treatment. We have studied the development of antiestrogen resistance in v...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90104-e
更新日期:1992-12-01 00:00:00
abstract::The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal trans...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2007.08.010
更新日期:2008-05-14 00:00:00
abstract::Compromise of gastric inhibitory polypeptide (GIP) receptor signalling represents a possible therapeutic strategy for the treatment of obesity-related diabetes. This study has characterised and evaluated the C-terminally fatty acid derivatised GIP analogues, GIP(3-30)Cex-K(40)[Pal] and Pro(3)GIP(3-30)Cex-K(40)[Pal], a...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2014.10.025
更新日期:2015-02-05 00:00:00
abstract::Prostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins. Because we recently found functional HSEs in the human and rodent c-fos promoters, we hypothesized that PGA1 might increase c-fos expression through the H...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00241-0
更新日期:2000-06-01 00:00:00
abstract::Pro-protein convertase-2 (PC2) and carboxypeptidase-E (CPE) proteins are two major members of the pro-protein convertases that involve in the maturation of protein precursor. By using PC2 activity, immunocytochemistry (ICC) and Western blot method, PC2, CPE and preproNPY protein expression levels were compared among m...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.01.020
更新日期:2009-05-06 00:00:00
abstract::Autodigestion of nuclei isolated from the androgen-dependent Shionogi mouse mammary carcinoma revealed the presence of endogenous endonuclease activity which was stimulated by Ca2+ and Mg2+ and generated a repeating pattern of DNA fragments with an average monomeric size of 179 base pairs. The nuclear concentration of...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(86)90144-9
更新日期:1986-05-01 00:00:00
abstract::The relationship between the structure of human growth hormone (hGH) and the hormone-receptor interaction has been investigated using as probes monoclonal antibodies (Mabs) to hGH of defined epitope specificity profile. Seven high affinity Mabs were studied for their ability (i) to inhibit the binding of 125I-hGH to N...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(89)90230-x
更新日期:1989-11-01 00:00:00
abstract::It has recently been shown that mammals contain a gene encoding a protein that is related to stanniocalcin (STC), a hormone previously considered to be present only in bony fish where it plays a major role in Ca2+ homeostasis. Here we report the identification in the mouse and human of a cDNA, STC-2, that shows signif...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00097-5
更新日期:1998-06-25 00:00:00
abstract::The metabolism of radioactive testosterone, 5alpha-dihydrotestosterone, 4-androstene-3beta,17beta-diol or 4-androstene-3alpha,17beta-diol by the human cell line NHIK 3025, derived from a carcinoma of the uterine cervix, was studied. The cells were grown in Eagle's minimal essential medium (MEM) with a steriod concentr...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(77)90003-x
更新日期:1977-10-01 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in stimulating insulin release in the pancreas as well as inhibiting gastric acid secretion in the stomach. GIP has been found in specific endocrine cells located in the mucosal layer of the small intestine and in the submandibular salivary gla...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(99)00106-9
更新日期:1999-08-20 00:00:00
abstract::Porcine Leydig cells in primary culture were incubated to equilibrium with increasing doses of either porcine luteinizing hormone (pLH) or human chorionic gonadotropin (hCG). Then, free and total high affinity gonadotropin receptors on the cell surface were dosed with [125I]hCG as tracer. In isotonic high salt medium,...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(91)90263-r
更新日期:1991-04-01 00:00:00
abstract::Urine based gonadotropin assays provide a practical means of analyzing hormone secretion patterns. While research protocols have revealed pulsatile patterns of gonadotropins such as LH in the blood, these assays are of limited clinical use since daily venipuncture sampling is not feasible outside of a research environ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2006.02.020
更新日期:2007-01-02 00:00:00
abstract::Several common KCNQ1 gene polymorphisms have been associated with the risk of type 2 diabetes (T2DM) and diabetic nephropathy. This effect is explained by the role of the kcnq1 protein as a potassium channel that in the pancreatic beta-cells drives an electrical signal that facilitates glucose-stimulated insulin secre...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.03.007
更新日期:2016-05-15 00:00:00
abstract::The heterodimeric 'pregnancy-specific' hormone human chorionic gonadotropin (hCG) has been used as the basis for a contraceptive vaccine. More recently, the observation that hCG, particularly in the form of the beta-chain expressed in the absence of alpha-chain, is aberrantly expressed in a number of different tumors ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2006.02.018
更新日期:2007-01-02 00:00:00
abstract::The availability of regulatory sequences directing tissue-specific expression of transgenes in genetically modified mice and large animals is a prerequisite for the development of adequate models for human diseases. The rat insulin 2 gene (Ins2) promoter, widely used to achieve transgene expression in pancreatic beta-...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.08.001
更新日期:2010-02-05 00:00:00
abstract::After the luteinizing hormone (LH) surge, the cells that remain from the ovulated follicle undergo a process of differentiation termed luteinization. Two key features of the cells after luteinization are the capacity for tremendous production of progesterone [10(16) molecules of progesterone per (min/(g of CL))] and t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(02)00056-4
更新日期:2002-05-31 00:00:00
abstract::Expression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet beta cells, but not in exocrine or alpha cells, suggesting a role for Pdzd2 in the regulation of pancreatic beta-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homo...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.11.007
更新日期:2010-02-05 00:00:00
abstract::Vitelline membrane outer layer protein 1 (VMO1), a basic protein present in the outer layer of the vitelline membrane of eggs, plays essential roles in separating the yolk from the egg white and preventing infection from bacteria by forming a barrier of fibrous layers in avian eggs. Although VMO1 is expressed in the o...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2014.10.015
更新日期:2015-01-05 00:00:00
abstract::We studied the functional properties of hepatic glucagon receptors during rat development. Glucagon binding to liver membranes and isolated hepatocytes was significantly less in foetuses and weaning rats than in adult animals, reflecting changes in the number of receptors rather than any change in receptor affinity fo...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(87)90208-5
更新日期:1987-02-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1-R (PACAP type 1 receptor) are transiently expressed in granulosa cells (GCs) of mouse preovulatory follicles and affect several parameters associated with the ovulatory process. We investigated the expression of PACAP and its receptors in...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2013.05.006
更新日期:2013-08-15 00:00:00
abstract::The Klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends lifespan when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate and vi...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2008.10.052
更新日期:2009-02-05 00:00:00
abstract::We find that completion of the first meiotic division in Rana pipiens oocytes requires the sequential action of at least two steroids: progesterone and one or more subsequent polar metabolites of progesterone. Progesterone binding in vitro to oocyte surface receptors increases during the first 4-5h of exposure, follow...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2008.05.013
更新日期:2008-09-10 00:00:00
abstract::An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offsprin...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.03.019
更新日期:2018-10-15 00:00:00
abstract::Cell-cell interactions are crucial role for the proper functioning of endocrine glands. We recently demonstrated that interactions of chromaffin and cortical cells are important for adrenocortical steroidogenesis. However, the molecular mechanisms have not been elucidated and it is unclear if this involves acute and/o...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00267-7
更新日期:2000-07-25 00:00:00
abstract::Glucose uptake by brown adipose tissue, measured following deoxyglucose injection in vivo, was increased by 6- and 11-fold following 2 and 14 days of cold exposure, respectively. To look for the possible mechanism of these modifications, the glucose transporter Glut 4 has been characterized at the protein and mRNA lev...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(92)90205-k
更新日期:1992-11-01 00:00:00
abstract::Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estro...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.04.007
更新日期:2018-11-15 00:00:00
abstract::Pasireotide has been associated with tumor shrinkage in patients with Cushing's disease subjected to long term treatment. However, to date the implicated molecular mechanisms are poorly elucidated. Here, we tested pasireotide-mediated cytostatic and cytotoxic effects in ACTH-secreting primary tumor cultures and murine...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.12.022
更新日期:2019-03-01 00:00:00
abstract::Emerging evidence shows a beneficial effect of estrogens for Parkinson's disease, yet the exact potency of these compounds implicated remain obscured. In this study, we investigated the neuroprotective effect of 17beta-estradiol and estrone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2008.07.019
更新日期:2008-12-16 00:00:00
abstract::Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci re...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2010.10.012
更新日期:2011-01-30 00:00:00
abstract::Three chimeras of the rat GnRH receptor (rGnRHR) and an enhanced green fluorescent protein (GFP) were assessed to examine their suitability as probes of the receptor in transfected GH3 cells. Direct fusion of GFP to the N or C terminus of the rGnRHR abolished the receptor ligand binding affinity and the chimeric recep...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00204-4
更新日期:1998-11-25 00:00:00