Abstract:
:A novel class of targeted chemotherapeutic agents based on cytotoxic compounds linked to LHRH analogs was tested in a long term superfusion system in order to determine their effects on different types of rat pituitary cells. The compounds investigated included two cytotoxic LHRH agonists, T-98 ([D-Lys6]LHRH coupled to glutaryl-2-(hydroxymethyl)anthraquinone (G-HMAQ)) and T-107 ([D-Lys6]LHRH linked to doxorubicin (DOX) through glutaric acid spacer), and two cytotoxic LHRH antagonists T-121 and T-144, both containing two residues of G-HMAQ. The analogs were infused for 24 h at pharmacological (micromolar) concentrations. The secretions of LH, GH, and PRL cells after a short (2-h) and a long (20-h) recovery period following the treatment were compared to those before the analog infusion. All four cytotoxic LHRH analogs selectively decreased the stimulated LH response, while basal secretions of LH, GH, and PRL as well as the stimulated release of GH and PRL were not influenced in spite of the high doses applied and the long duration of exposure. The inhibitory effects of cytotoxic agonists and antagonists were significantly greater than those of their parent peptides. Equimolar concentrations of cytotoxic compounds alone (DOX or G-HMAQ), however, caused functional damage to all types of cells tested. To evaluate the mechanisms of the observed inhibitory actions, we compared the amount of LH released in response to 1) a specific stimulus to receptors (3 nM LHRH), 2) membrane depolarization with 100 MM KCl, not involving the receptor, and 3) the extraction of cells with 0.01 N HCl at the end of experiment. Cytotoxic LHRH agonists and their carriers caused depletion of LH pools, while cytotoxic LHRH antagonists or their parent peptides decreased the available binding sites for LHRH. The inhibitory effect of DOX on stimulated secretion of LH, GH, and PRL in our system could be due to an action on cell membranes. Our work indicates that in the pituitary cell superfusion system, targeted cytotoxic conjugates, based on LHRH analogs, selectively affect LH cells, in contrast to unconjugated cytotoxic compounds, which also damage GH and PRL cells.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Rékási Z,Szöke B,Nagy A,Groot K,Rékási ES,Schally AVdoi
10.1210/endo.132.5.8477650subject
Has Abstractpub_date
1993-05-01 00:00:00pages
1991-2000issue
5eissn
0013-7227issn
1945-7170journal_volume
132pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::The time sequence of the metabolism of [4-14C] pregnenolone to testosterone in homogenates of human and rat testis was studied with special emphasis on the chain of events in the early 15 min of incubation. The incubations were performed at 32 C in the presence of NAD and a NADPH-generating system. The various interme...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-5-1909
更新日期:1987-05-01 00:00:00
abstract::We looked for the presence of vitamin D-dependent intestinal calcium binding protein (CaBP), relative molecular mass (mol wt) about 10,000, in kidneys of mammals, birds, and reptiles, and compared the localization of this 10,000 mol wt CaBP with the localization of the 28,000 mol wt vitamin D-dependent CaBP. Antiserum...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-2-674
更新日期:1985-08-01 00:00:00
abstract::Somatostatin-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in rat thyroid parafollicular cells. Studies were therefore performed to determine whether SRIF-LI was present in a transplantable medullary carcinoma of the thyroid (MCT) in the WAG/Rij strain of rat. SRIF-LI was found...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-107-5-1418
更新日期:1980-11-01 00:00:00
abstract::Uterine ornithine decarboxylase (ODC) activity is reported to increase after estrogen administration to fetal, neonatal, immature, and adult rats, suggesting that it may be a useful marker in studies of the development of estrogen responsiveness. Standard conditions were validated for enzyme assay of uterine cytosols ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-5-1826
更新日期:1983-11-01 00:00:00
abstract::In the present study, steroidogenesis in two different Leydig tumor cell lines was compared. One, the MA-10 mouse tumor cell line, produces steroids and the steroidogenic acute regulatory (StAR) protein only when stimulated by trophic hormones and cAMP analogs. The other, the R2C rat tumor cell line, produces steroids...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-0941
更新日期:2004-12-01 00:00:00
abstract::The two phases of the ovulatory menstrual cycle of the primate are characterized by divergent activities of the GnRH pulse generator. During the luteal phase, LH pulse frequency is significantly reduced below that observed during the follicular phase. In this report we investigate whether the decrease in pulse frequen...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-5-2044
更新日期:1987-05-01 00:00:00
abstract::A miniature thermoelectric probe was used to record continuously tissue blood flow in the anterior pituitary gland of anesthetized dogs. The output of the flow probe is linear in the range of tissue blood flow encountered in the pituitary. Probe placement required minimal tissue trauma, and zero blood flow was recorde...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-97-3-630
更新日期:1975-09-01 00:00:00
abstract::Estradiol (E) treatment of spayed macaques induces progestin receptors (PR) in pituitary gonadotropes, but not lactotropes. In contrast, levels of pituitary estrogen receptors (ER) remain constant in spayed or E-treated monkeys. In monkey pituitary cultures, the number of PR-positive cells varies depending on the dono...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-4-1907
更新日期:1991-04-01 00:00:00
abstract::During lung development there is tension between positive and negative regulators of fibroblast-epithelial communication controlling type II cell differentiation. A clinical consequence of imbalance of this tension is the increased risk for respiratory distress syndrome in male infants. We hypothesized that chronic in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.8.7615
更新日期:2000-08-01 00:00:00
abstract::To determine the effect of aromatase inhibitors on peripheral aromatization, male rhesus monkeys were infused with [7-3H]androstenedione and [4-14C]estrone before and during treatment with 4-hdyroxy-androstene-3,17-dione (50 mg/kg each; four monkeys) or 4-acetoxy-androstene-3,17-dione (700 mg each; two monkeys). In al...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-106-1-19
更新日期:1980-01-01 00:00:00
abstract::The master circadian clock located within the hypothalamic suprachiasmatic nucleus (SCN) is necessary for the circadian rhythm of glucocorticoid (GC) release. The pathways by which the SCN sustains rhythmic GC release remain unclear. We studied the circadian regulation of cortisol release in the behaviorally split gol...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1624
更新日期:2012-02-01 00:00:00
abstract::To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1655
更新日期:2008-06-01 00:00:00
abstract::Glutathione (GSH) is the most abundant intracellular thiol and an important regulator of cellular redox status. Mice that lack the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH synthesis. Nicotinamide nucleotide transhydrogenase, an inner mitochondr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-0207
更新日期:2011-07-01 00:00:00
abstract::A series of rat and mouse monoclonal antibodies to the human progesterone receptor (PR) has recently been produced. These antibodies were used for the immunocytochemical identification of PR in several mammalian species including humans. The specificity of the monoclonal antibodies for PR was confirmed by using compet...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-3-1165
更新日期:1988-03-01 00:00:00
abstract::The adipokine, leptin (LEP), is a hormonal gateway, signaling energy stores to appetite-regulatory neurons, permitting reproduction when stores are sufficient. Dual-labeling for LEP receptors (LEPRs) and gonadotropins or GH revealed a 2-fold increase in LEPR during proestrus, some of which was seen in LH gonadotropes....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1132
更新日期:2014-10-01 00:00:00
abstract::In the present study we used characterized perifusion model for the development of homologous desensitization to GnRH in the pituitary gonadotrope. This system relies on immobilized primary pituitary cultures that are perifused with various pulse patterns and concentrations of GnRH; these patterns and concentrations a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.5.8612520
更新日期:1996-05-01 00:00:00
abstract::GH and IGF-I are potent regulators of muscle growth and function. Although IGF-I is known to mediate many of the effects of GH, it is not yet clear whether all effects of GH are completely dependent on the IGF-I system. To evaluate the biological effects of the GH/IGF-I axis on muscle growth, we administrated recombin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-0906
更新日期:2005-04-01 00:00:00
abstract::Regulation of galanin gene expression in the anterior pituitary (AP) is positively influenced by estrogen in rodents and undetermined in humans. The objective of this study was to investigate the mechanism behind estrogen induction of galanin by identifying any putative estrogen receptor (ER) binding sequences within ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.11.5507
更新日期:1997-11-01 00:00:00
abstract::Brief exposure of male rats to estrogens during the neonatal period interrupts normal prostate development, alters epithelial cell differentiation, and predisposes this gland to hyperplasia and severe dysplasia analogous to prostatic intraepithelial neoplasia (PIN) with aging. Previous work demonstrated that the reduc...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0035
更新日期:2003-11-01 00:00:00
abstract::Rat epididymal fat cells were isolated and incubated with 25 microunits insulin/ml for 15 minutes. Insulin induced a significant shift in the saturated/unsaturated fatty acid ratio of the cerebroside fraction isolated from fat cell ghosts. This change was due to a decrease of saturated fatty acids and an increase of u...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-5-2014
更新日期:1981-05-01 00:00:00
abstract::We reported previously that chromogranin A (Chga) knockout (KO) mice are hypertensive and hyperadrenergic. Here we sought to determine the basis of such alterations by probing physiological, biochemical, and pharmacological responses to perturbations of the autonomic nervous system. In the conscious state, KO mice had...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0429
更新日期:2009-11-01 00:00:00
abstract::The role of nutrients and hormones in the regulation of glucagon release is investigated in pancreatic A cells purified by autofluorescence-activated cell sorting. Purified A cells lack secretory activity in 1-h incubation at 1.4 mM glucose. Their release mechanism can be activated by arginine, alanine, and glutamine,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-3-817
更新日期:1985-09-01 00:00:00
abstract::Light and electron microscopic triple immunostaining was performed on coronal vibratome sections prepared from the hypothalamus of ovariectomized (OVX) and OVX plus estrogen-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for progesterone receptors (PRs) and neuropeptide-Y (NPY) was visualized...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.1.8100520
更新日期:1993-07-01 00:00:00
abstract::To investigate the mechanism of insulin insensitivity during fasting and hyperresponsiveness to insulin after refeeding, insulin binding, 2-deoxyglucose uptake and glucose oxidation were measured in adipocytes from three groups of rats: control, 48 h fasted, and 48 h refed after 48 h fasting. In 48 h fasted rats, fat ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-100-5-1384
更新日期:1977-05-01 00:00:00
abstract::These experiments queried the potential for developmental change in the positive and negative feedback sensitivities of LH secretion to estradiol. Serum LH levels were compared in juvenile, peripubertal, and adult female mice after ovariectomy and challenge with a variety of 4-day steroid treatments. Since male stimul...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-2-506
更新日期:1981-02-01 00:00:00
abstract::GH is an important regulator of body growth and composition as well as numerous other metabolic processes. In particular, liver plays a key role in the GH/IGF-I axis, because the majority of circulating "endocrine" IGF-I results from GH-stimulated liver IGF-I production. To develop a better understanding of the role o...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-2086
更新日期:2014-05-01 00:00:00
abstract::Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene cause central hypothyroidism. IGSF1 is a transmembrane glycoprotein of unknown function expressed in thyrotropin (TSH)-producing thyrotrope cells of the anterior pituitary gland. The protein is cotranslationally cleaved, with ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1788
更新日期:2017-04-01 00:00:00
abstract::Adenylate cyclase of rat renal cortex was inhibited by angiotensin II (AII). Inhibition required Na+ (100-200 mM) and GTP (10(-8)-10(-4) M) and was opposed by the receptor antagonist [1-sarcosine, 8-isoleucine]AII. The EC50 value (+/- SE)for inhibition by AII was 3.7 +/- 1.2 nM, and the maximum inhibition (+/- SE) was...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-111-5-1687
更新日期:1982-11-01 00:00:00
abstract::Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1288
更新日期:2011-11-01 00:00:00
abstract::In mammals, adrenal medulla chromaffin cells constitute a fundamental component of the sympathetic nervous system outflow, producing most of the circulating adrenaline. We recently found that the rhesus monkey adrenal gland expresses several genes in a 24-h rhythmic pattern, including TH (the rate-limiting enzyme in c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0610
更新日期:2007-12-01 00:00:00