Abstract:
:L-Asparaginase (ASNase), a drug widely used in the treatment of acute lymphoblastic leukemia, has been reported to decrease serum T4-binding globulin (TBG) levels, while results of serum albumin determinations were conflicting. This effect in vivo has been attributed to depressed liver protein synthesis, but this hypothesis has not been proved. To investigate this problem, human hepatoma (Hep G2) cells were continuously labeled for 4 h with 100 microCi/ml [35S]methionine in the absence or presence of graded amounts of ASNase (from 0.1 nM to 0.1 mM). Media and cell lysates were collected, immunoprecipitated with antialbumin or anti-TBG serum and protein A, and submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were sliced, and the radioactivity was counted in a beta-counter. A dose-dependent inhibition of TBG and albumin biosynthesis (as well as of total protein synthesis) was demonstrable, but TBG appeared to be more sensitive to the action of the drug. In fact, TBG biosynthesis was reduced by 8% with 0.1 nM ASNase, while an effect on albumin was observed only at 1 nM ASNase; 50% inhibition was obtained with 30 nM ASNase in the case of TBG and with 800 nM in the case of albumin. At the highest concentration (0.1 mM), TBG biosynthesis was reduced by 94%, and albumin biosynthesis by 75%. ASNase also proved to have a time-dependent effect, as assessed by the measurement of radioimmunoassayable TBG in the media from Hep G2 cells grown in the presence of 10 nM ASNase for 1-4 days. The TBG concentration was progressively reduced, by 40% after 1 day to 85% after 4 days. In pulse-chase experiments, a reduction of total (intracellular plus secreted) immunoprecipitable TBG and, to a lesser extent, albumin was observed, suggesting that the drug also affected the catabolism of newly synthesized proteins. These results provide the first in vitro evidence that ASNase actually inhibits TBG biosynthesis. This effect is not specific for TBG, but this protein appears to be more susceptible than albumin to ASNase action. This can explain why in patients treated with ASNase for leukemia, a decrease in serum TBG concentrations has not always been associated with a reduction in serum albumin levels.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Bartalena L,Martino E,Antonelli A,Pacchiarotti A,Robbins J,Pinchera Adoi
10.1210/endo-119-3-1185subject
Has Abstractpub_date
1986-09-01 00:00:00pages
1185-8issue
3eissn
0013-7227issn
1945-7170journal_volume
119pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Previous studies showed that noncalcemic 20(OH)D3, a product of CYP11A1 action on vitamin D3, has antifibrotic activity in human dermal fibroblasts and in a bleomycin mouse model of scleroderma. In this study, we tested the role of retinoic acid-related orphan receptor γ (RORγ), which is expressed in skin, in the acti...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa198
更新日期:2021-01-01 00:00:00
abstract::Maintenance of FSH biosynthesis requires ongoing exposure to pulsatile GnRH. Recent data demonstrate that activin also stimulates FSH biosynthesis. We used a perifused pituitary system to examine regulation of FSH beta mRNA levels by pulsatile GnRH and activin. Hourly pulses of 10 nM GnRH increased FSH beta mRNA level...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.3.1505470
更新日期:1992-09-01 00:00:00
abstract::Decidualization, the process by which fibroblastic human endometrial stromal cells (HESC) differentiate into secretory decidual cells, is a critical event during the establishment of pregnancy. It is dependent on the steroid hormone progesterone acting through the nuclear progesterone receptor (PR). Previously, we ide...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqz021
更新日期:2020-01-01 00:00:00
abstract::Historically, much of the research on health effects of environmental pollutants focused on ascertaining whether compounds were carcinogenic. More recent findings show that environmental contaminants also exert insidious effects by disrupting hormone action. Of particular concern are findings that developmental exposu...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2005-1157
更新日期:2006-06-01 00:00:00
abstract::Atrial, brain-type, and C-type natriuretic peptides (ANP, BNP, and CNP) act via receptors with intrinsic guanylate cyclase activity. The A-type and B-type ANP receptors are selectively activated by ANP and CNP, respectively. The anterior pituitary is a site of ANP production and action, suggesting a local regulatory f...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.5.7682940
更新日期:1993-05-01 00:00:00
abstract::We have recently identified gonadotropes as target cells for ATP action via ATP receptors of the P2U subtype. The present studies have used gonadotrope-derived alpha T3-1 cells to examine the possible signaling mechanisms subserving ATP action in gonadotropes. Addition of ATP produced a biphasic intracellular Ca2+ (Ca...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.1.8536620
更新日期:1996-01-01 00:00:00
abstract::Hyperactivation of the GHRH receptor or downstream signaling components is associated with hyperplasia of the pituitary somatotrope population, in which adenomas form relatively late in life, with less than 100% penetrance. Hyperplastic and adenomatous pituitaries of metallothionein promoter-human GHRH transgenic (Tg)...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-1482
更新日期:2009-07-01 00:00:00
abstract::LH treatment of isolated medium (3- to 7-mm) follicles from porcine ovaries stimulated pregnenolone synthesis by mitochondria isolated from these tissues. This LH stimulation of pregnenolone synthesis was observed regardless of whether exogenous cholesterol was added to the mitochondrial assay system, suggesting that ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-114-2-588
更新日期:1984-02-01 00:00:00
abstract::The somatic Sertoli cells of the testis are major targets for FSH and are important for the regulation of spermatogenesis. The binding of FSH to Sertoli cells activates the cAMP-dependent protein kinase A signaling pathway, resulting in phosphorylation of the cAMP response element-binding protein (CREB), which is requ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.8.7628390
更新日期:1995-08-01 00:00:00
abstract::Apoptosis is a physiological process by which multicellular organisms eliminate unwanted cells. Death factors such as Fas ligand induce apoptosis by triggering a series of intracellular protein-protein interactions mediated by defined motifs found in the signaling molecules. One of these motifs is the death effector d...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.12.6335
更新日期:1998-12-01 00:00:00
abstract::The plasma osteocalcin (OC) concentration correlates with histological parameters of bone formation and has been used as an index of osteoblast activity. Although the rate of OC synthesis is likely to be a major determinant of the plasma OC level, the contribution of other processes, for example, OC plasma clearance, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-6-2785
更新日期:1989-06-01 00:00:00
abstract::Photoaffinity labeling with underivatized T3 was used to identify T3-binding proteins in the membrane of rat erythrocytes. UV irradiation of ghosts and peripheral protein-depleted membranes in the presence of [125I]T3 resulted in the covalent attachment of 125I to membrane proteins (analyzed by polyacrylamide gel elec...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.6.8504750
更新日期:1993-06-01 00:00:00
abstract::The atrial natriuretic peptide (ANP) gene is expressed in several extraatrial tissues in which ANP may be involved in the regulation of autocrine or paracrine functions. In the ovary, the synthesis of ANP, its binding sites, and a physiological role were found. The ANP system in the oviduct, however, is yet to be defi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.6.5160
更新日期:1997-06-01 00:00:00
abstract::GH feeds back at the level of the central nervous system to alter the release of somatostatin and GRF, resulting in altered GH release. The purpose of this study was to see whether the concentration of GH, impinging directly on the somatotrophs of the adenohypophysis, would alter the responsiveness of the somatotrophs...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-4-1511
更新日期:1988-04-01 00:00:00
abstract::In mammals, skeletal muscle mass is negatively regulated by a muscle-derived growth/differentiating factor named myostatin (MSTN) that belongs to the transforming growth factor-beta superfamily. Although putative MSTN homologs have been identified from several vertebrates, nonmammalian orthologs remained poorly define...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.4.8097
更新日期:2001-04-01 00:00:00
abstract::The effects of K+ depletion and ouabain (0.1, 0.5, and 1 mM) on glucagon and insulin release from the in vitro perfused rat pancreas were studied in the absence or presence of arginine (10 mM). In the absence of arginine, K+ depletion resulted in an inhibition of glucagon release, both at a low (2.8 mM) and a higher (...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-1-178
更新日期:1983-07-01 00:00:00
abstract::In vivo and in vitro evidence indicates that FSH is a primary regulator of testicular inhibin production. However, recent reports suggest that LH may also promote inhibin secretion in vivo. To investigate whether LH regulates inhibin subunit messenger RNA (mRNA) expression as well, we examined the effects of hypophyse...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-3-1097
更新日期:1990-09-01 00:00:00
abstract::The molecular links between membrane excitability and neurohormone synthesis were investigated using a simple model system: the bag cell neurons of Aplysia. We tested the hypothesis that the electrical afterdischarge, which leads to depletion of egg-laying hormone (ELH) by triggering secretion, rapidly stimulates ELH ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.12.6350
更新日期:1998-12-01 00:00:00
abstract::The corpora lutea of pregnancy in the rat are highly dependent on the action of PRL and PRL-like hormones to hypertrophy and to produce progesterone needed for the maintenance of gestation. Two forms of the PRL receptor (PRL-R), designated as long (PRL-RL) and short (PRL-RS), have been described in rat tissues. To det...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.11.5479
更新日期:1997-11-01 00:00:00
abstract::The effects of dopamine on PRL secretion and lysosomal enzyme activity in anterior pituitary tissue from rats selected during various stages of the estrous cycle were examined under in vitro conditions. During the estrous cycle, there was a marked variation in the capacity of dopamine to stimulate the activity of the ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-3-903
更新日期:1981-03-01 00:00:00
abstract::The amount of corticosterone bound to proteins in the adenohypophysis and dorsal hippocampus was studied concurrently with the plasma ACTH concentration in 4-week adrenalectomized male rats under steady-state conditions achieved by infusing the steroid at a constant rate for 45 min. Corticosterone binding was measured...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-97-1-223
更新日期:1975-07-01 00:00:00
abstract::The localization of calcitonin gene-related peptide (CGRP)-like immunoreactivity in the adrenal gland of the frog, Rana ridibunda, was examined by the indirect immunofluorescence technique. Using an antiserum directed against rat alpha-CGRP, the presence of a network of positive fibers was observed in the adrenal pare...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.1.8013380
更新日期:1994-07-01 00:00:00
abstract::To determine the relationship between the concentrations of serum T3 and hepatic nuclear T3 receptor in a reversible nonthyroidal disease, we studied these parameters in rats with streptozotocin-induced diabetes mellitus, control rats, and rats that were weight-matched to the diabetic rats by food restriction. Results...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-109-4-1259
更新日期:1981-10-01 00:00:00
abstract::Reactive oxygen species, such as superoxide, hydrogen peroxide, and lipid peroxides, impair luteal function. Vitamin E, a lipophilic antioxidant vitamin, provides a major avenue of protection by scavenging free radicals and terminating lipid peroxidation. We previously showed that ovarian vitamin E levels increase aft...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.2.8033800
更新日期:1994-08-01 00:00:00
abstract::Intraluteal infusion of the prostaglandin (PG) synthesis inhibitor, sodium meclofenamate (Mec) causes premature luteolysis in rhesus monkeys. To evaluate further the actions of PG synthesis inhibitors in primate luteal function, we examined the in vitro effects of Mec and another inhibitor, flurbiprofen (Flur), on PG,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-3-1380
更新日期:1990-03-01 00:00:00
abstract::The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues and organs, including the pituitary. However, there is no information...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0116
更新日期:2009-10-01 00:00:00
abstract::The pregnancy hormone relaxin has recently been shown to be cardio-protective. Despite its well-established antifibrotic actions in the heart, the effects of relaxin on cardiomyocytes (CM) remain to be determined. We investigated effects of isoform 2 of the human relaxin (H2-relaxin) on CM hypertrophy and apoptosis. I...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-1324
更新日期:2007-04-01 00:00:00
abstract::To analyze the molecular origin of an ER variant, the truncated ER product-1, transiently expressed at the proestrus in lactotrope cells, we generated a 2.5-kb sequence of a genomic region upstream and downstream the specific sequence truncated ER product-1. Genomic Southern blot analysis showed that truncated ER prod...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.9.8392
更新日期:2001-09-01 00:00:00
abstract::Retinoids induce cellular differentiation and inhibit cellular proliferation. Proliferation of human breast carcinoma cells in vitro is markedly inhibited by these compounds. On the other hand, insulin-like growth factors (IGFs) and their receptors seem to be involved in the growth of certain breast carcinoma cells by...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-2-1115
更新日期:1991-02-01 00:00:00
abstract::Most studies of lipoprotein requirements for steroid secretion by the adrenal have examined the mixed cell population of the whole gland; none have examined lipoprotein requirements of guinea pig adrenocortical cells. In this study the effect of exogenous lipoprotein on the ability of cells from each of the different ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-2-640
更新日期:1987-02-01 00:00:00