Abstract:
BACKGROUND:Activation of somatostatin receptors (sstr1-5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing's disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. METHODS:We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. RESULTS:All mAbs were highly specific with no cross-reactivity. The sstr1-5 immunoreactivity in gastrointestinal NET (n=67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. CONCLUSION:Determination of the sstr1-5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
Schmid HA,Lambertini C,van Vugt HH,Barzaghi-Rinaudo P,Schäfer J,Hillenbrand R,Sailer AW,Kaufmann M,Nuciforo Pdoi
10.1159/000330616subject
Has Abstractpub_date
2012-01-01 00:00:00pages
232-47issue
3eissn
0028-3835issn
1423-0194pii
000330616journal_volume
95pub_type
杂志文章abstract:BACKGROUND:We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. METHODS:Patients with advan...
journal_title:Neuroendocrinology
pub_type: 杂志文章,多中心研究
doi:10.1159/000479587
更新日期:2018-01-01 00:00:00
abstract:CONTEXT:Early pubertal luteinizing hormone (LH), and by inference gonadotropin-releasing hormone (GnRH), pulse secretion is marked by high nocturnal but low daytime frequency; however, the underlying mechanisms remain unclear. Plasma concentrations of progesterone, the major regulator of GnRH frequency in women, increa...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000336395
更新日期:2012-01-01 00:00:00
abstract::Previous work has demonstrated that N-methyl-D-aspartate (NMDA) is capable of stimulating luteinizing hormone release in a variety of species. Interestingly, the ability of NMDA to stimulate luteinizing hormone release is significantly compromised in castrated male and female rats as compared to intact animals. The pu...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126607
更新日期:1993-12-01 00:00:00
abstract::This study was carried out to clarify the central effects of neuropeptide Y (NPY) on gonadotropin and prolactin (PRL) release in the male rat and to evaluate the hypothesis that it may play a role in negative feedback regulation of gonadotropin secretion in the male. NPY (4 micrograms in 2 microliters 0.9% NaCl) or an...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126481
更新日期:1993-06-01 00:00:00
abstract::The effect of in vivo corticosterone manipulation on binding sites for the excitatory neurotransmitter glutamate was determined using radioligand binding to rat brain cryostat sections and crude synaptic membranes. 3H-glutamate binding to regions of the dorsal hippocampal formation was significantly decreased in adren...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125017
更新日期:1988-09-01 00:00:00
abstract:BACKGROUND/AIMS:Cervical stimulation induces a circadian rhythm of prolactin secretion and antiphase dopamine release. The suprachiasmatic nucleus (SCN) controls this rhythm, and we propose that it does so through clock gene expression within the SCN. METHODS:To test this hypothesis, serial blood samples were taken fr...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000254379
更新日期:2010-01-01 00:00:00
abstract::Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (C...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126787
更新日期:1994-11-01 00:00:00
abstract::Delta-sleep-inducing peptide (DSIP) colocalizes within gonadotropin-releasing-hormone (GnRH)-containing neurons in adult hypothalamus and could play a role in the regulation of hypothalamic-pituitary axis in adults. To support the possibility that DSIP also participates in fetal neuroendocrine events and to demonstrat...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126098
更新日期:1992-01-01 00:00:00
abstract::To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) a...
journal_title:Neuroendocrinology
pub_type: 临床试验,杂志文章
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更新日期:2003-07-01 00:00:00
abstract::Male Turkish hamsters received horizontal knife cuts within the hypothalamus to investigate the role of afferent and efferent projections of the paraventricular nucleus (PVN) in seasonal regulation of endocrine function. Following surgery, the animals were exposed to either a long (16 h light/8 h dark) or a short (8 h...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126159
更新日期:1992-04-01 00:00:00
abstract::Estrogens are crucial determinants in the regulation of anterior pituitary function and maintenance of tissue homeostasis. Estrogen actions in this gland are exerted through both classical and non-classical mechanisms of action. This review summarizes the expression of classical α- and β-estrogen receptors and variant...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00
abstract::The effects of corticotropin-releasing factor (CRF) on GnRH release from the adult male rat mediobasal hypothalamus (MBH) and median eminence (ME) were studied in an in vitro incubation system. CRF induced a dose-related inhibition of GnRH release from both the MBH and the isolated ME, and this inhibition was blocked ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124578
更新日期:1986-01-01 00:00:00
abstract::We have previously reported that the somatotropin regulatory peptides, growth hormone-releasing hormone (GRF) and somatostatin (SS) increase feeding when applied centrally in low picomole-range doses. The similarity between the dose-response characteristics and photoperiod sensitivities of these two peptide's feeding ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126372
更新日期:1993-01-01 00:00:00
abstract::Endogenous gonadoliberin was localized by using immunocytological methods in the hypothalamic neurons which synthetize the peptide and in the hypophysial target cells. The rat tissues were fixed and frozen. Ultrathin sections were obtained by cryoultramicrotomy. In the pituitary gland, GnRH was observed in both gonado...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123300
更新日期:1982-03-01 00:00:00
abstract::Structural and functional impairment of the skeletal system remains an important cause of morbidity and disability in patients with Cushing's syndrome (CS). Glucocorticoid (GC) excess inhibits bone formation and calcium absorption from the gut, increases bone resorption, and alters the secretion of gonadotropin and gr...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000314298
更新日期:2010-01-01 00:00:00
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journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124668
更新日期:1986-01-01 00:00:00
abstract::Endocrine pancreatic tumours (EPTs) are uncommon, with a major challenge to alert physicians to their recognition and requirements of treatment. Functioning EPTs cause well-known clinical syndromes of hormone excess. Insulinomas, gastrinomas and glucagonomas are most common; vipomas and somatostatinomas are rare. EPTs...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000080744
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND/AIMS:Stress exacerbates neuron loss in many CNS injuries via the actions of adrenal glucocorticoid (GC) hormones. For some injuries, this GC endangerment of neurons is accompanied by greater immune cell activation in the CNS, a surprising outcome given the potent immunosuppressive properties of GCs. METHODS...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000367849
更新日期:2014-01-01 00:00:00
abstract::The orphanin-FQ/nociceptin (OFQ/N) receptor (previously, ORL1, LC132) has been shown to be coupled to an inwardly rectifying K+ conductance in several neuronal populations. Although OFQ/N receptor mRNA is densely expressed in the supraoptic nucleus (SON), little is known about its coupling to effector system(s). The p...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054441
更新日期:1999-05-01 00:00:00
abstract::Several molecular forms related to the decapeptide LHRH were characterized and quantified in various brain structures of intact and castrated male and female rats. Distinct moieties were separated by high performance liquid chromatography (HPLC) and radioimmunoassayed against anti-LHRH antibodies of different specific...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126539
更新日期:1993-08-01 00:00:00
abstract::Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous r...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126989
更新日期:1995-07-01 00:00:00
abstract::Estradiol rapidly regulates the activity of arcuate nucleus (ARH) proopiomelanocortin (POMC) neurons that project to the medial preoptic nucleus (MPN) to regulate lordosis. Orphanin FQ/nociceptin (OFQ/N) acts via opioid receptor-like (ORL)-1 receptors to inhibit these POMC neurons. Therefore, we tested the hypothesis ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000443765
更新日期:2016-01-01 00:00:00
abstract::To further investigate the role of serotonin in human prolactin (Prl) secretion, serotonin antagonists have been administered to healthy volunteers in basal conditions and after pretreatment with the selective blocker of dopamine receptors, pimozide (Pim). Highly significant falls (p less than 0.001) in serum Prl were...
journal_title:Neuroendocrinology
pub_type: 临床试验,杂志文章
doi:10.1159/000122753
更新日期:1978-01-01 00:00:00
abstract::The caudal portion of the spinal cord of elasmobranch fish incorporates a diffuse neuroendocrine system. Using an antiserum raised against urotensin II from a teleost fish (goby) to facilitate purification, a peptide structurally related to urotensin II was isolated in pure form from an extract of neuroendocrine tissu...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126119
更新日期:1992-02-01 00:00:00
abstract::Hypophysitis is a relatively rare disease that exerts a strong autoimmune component encompassing different etiologies. Immunomodulatory drugs, such as interferon-α, are known to rarely induce hypophysitis. In recent years, a large number of new biological and immunomodulatory agents have been introduced into clinical ...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000480086
更新日期:2018-01-01 00:00:00
abstract::The level of thyroid hormone in blood has been acutely decreased by about 20--30% within 20 min with the aid of isovolemic exchange transfusion (IET) of thyroid hormone free blood cell suspension (THFBCS) in three groups of rats: (1) intact control (C); (2) median eminence (ME)-lesioned; (3) thalamus (TH)-lesioned. Th...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122711
更新日期:1977-01-01 00:00:00
abstract::To clarify the role and site of action of gamma-aminobutyric acid (GABA) in ovine pineal glands, we have investigated the effects of aminooxyacetic acid (AOAA), an inhibitor of GABA transaminase, on endogenous GABA content and beta-adrenoceptor mediated pineal function in Merino sheep. A significant elevation of endog...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000123892
更新日期:1984-03-01 00:00:00
abstract::Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive respo...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000328226
更新日期:2011-01-01 00:00:00
abstract::Acute electrolytic stimulation of the median raphe (MR) nucleus (MR Stim) between 13:00 and 16:00 h on proestrus blocked ovulation in 10 of the 21 rats tested, whereas all sham-treated (MR Sham, no current) animals ovulated normally (n = 12). MR Stim at 16:00 h on proestrus in individual cannulated rats 'turned off' t...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122884
更新日期:1979-01-01 00:00:00
abstract::To determine the possible physiological role of endogenous growth hormone-releasing factor (GRF) in the neuronal content and release of cerebral somatostatin (SS), we studied the effect of endogenous GRF blockade on the immunoreactive SS (IR-SS) content of cells and media in fetal rat cerebral cortical and hypothalami...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126118
更新日期:1992-02-01 00:00:00