Abstract：
:Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test whether some of the drugs currently used in their treatment, such as somatostatin analogues and mTOR inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only. We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1alpha under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by octreotide and rapamycin may contribute to their therapeutic effects.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
Villaume K,Blanc M,Gouysse G,Walter T,Couderc C,Nejjari M,Vercherat C,Cordier-Bussat M,Roche C,Scoazec JYdoi
10.1159/000289569subject
Has Abstractpub_date
2010-01-01 00:00:00pages
268-78issue
3eissn
0028-3835issn
1423-0194pii
000289569journal_volume
91pub_type
杂志文章abstract：:We have used excitatory amino acids as tools to elucidate changes in hypothalamic function associated with lactation, focusing on the regulation of luteinizing hormone (LH) and prolactin secretion. In these studies, we have compared the responsiveness to NMA (N-methyl-D,L-aspartate), an agonist for the N-methyl-D-aspa...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126576
更新日期：1993-10-01 00:00:00
abstract：:The known occurrence of opiates in the adrenals stimulated us to determine whether Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous peptide that can act as an antiopiate, is present in these glands and whether adrenalectomy affects its concentrations in plasma. The presence of Tyr-MIF-1 in the adrenals of the rat was sh...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126403
更新日期：1993-03-01 00:00:00
abstract：:The pressor effect of intravenous angiotensin II (AII) was compared in the unrestrained rat before and after electrolytic lesions of the subfornical organ (SFO), the circumventricular organ of the dorsal third cerebral ventricle. Abdominal aortic and venal caval catheters were used to measure arterial pressure and to ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000123107
更新日期：1980-12-01 00:00:00
abstract：:The neurotransmitter and andrenoceptors involved in the inhibition of luteinizing hormone (LH) release induced by stimulating the locus ceruleus nucleus (LC) have been characterized in ovariectomized, estrogen-primed rats in which the release of LH was triggered by electrical stimulation of the medial preoptic area. B...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000123858
更新日期：1984-01-01 00:00:00
abstract：:The possibility was investigated that centrally administered rat prolactin (PRL), i.e., intracerebroventricularly (ICV) or intrathecally (IT), may influence mammary contractility in urethane-anesthetized lactating rats. In addition to the monomer (23 kD PRL), the 16- and 7-kD PRL fragments were also tested and their e...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000127006
更新日期：1995-08-01 00:00:00
abstract：:The effect of frontal deafferentation of the medial basal hypothalamus on pro-opiomelanocortin (POMC) gene expression was studied in the intermediate lobe (IL) and anterior lobe (AL) of the pituitary gland in the absence and presence of corticosterone (CORT). The lesion in the basal hypothalamus removed neural inputs ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000124936
更新日期：1988-04-01 00:00:00
abstract：:Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be rel...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126236
更新日期：1992-08-01 00:00:00
abstract：:Acute immobilization stress results in changes in the concentration of both dopamine and noradrenaline in specific forebrain limbic system areas, whereas the adrenaline levels remain unchanged. Changes in dopamine concentrations are more restricted than those in noradrenaline concentrations. Dopamine levels are increa...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000123413
更新日期：1982-11-01 00:00:00
abstract：:17 alpha-hydroxyprogesterone (up to 200 mug/day) and 11 beta-hydroxyandrostenedione (up to 500 mug) had no effect on PMS-induced ovulation in intact immature rats. 10 mug/day of testosterone propoinate (TP) on days 28-30 of life decreased the percent of animals ovulating and the number of ova produced; this effect per...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000122338
更新日期：1975-01-01 00:00:00
abstract：:The properties of neuronal-type nicotinic acetylcholine receptors (nAChRs) present on the neuroendocrine cells of the porcine pars intermedia of the pituitary were studied in intact single cell using measurements of the free intracellular Ca2+ concentration ([Ca]i) with the calcium-sensitive dye fura 2. Local applicat...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126772
更新日期：1994-10-01 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：:The storage form of prolactin (PRL) was converted into the releasable form in the lactating rat pituitary gland within 10 min of suckling by 6 pups following 4-5 h of nonsuckling on postpartum day 13-14. The characteristics of the PRL discharge from the releasable pool into the circulation was then studied using a sti...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000123957
更新日期：1984-07-01 00:00:00
abstract：:The present study investigates the role of melanotrope proopiomelanocortin-derived peptide in the interrenal stress response to different stressors in male gilthead sea bream, Sparus aurata. Plasma cortisol and acetyl salmon endorphin (acetyl s-EP), as well as pituitary acetyl s-EP contents, were measured during two s...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000054359
更新日期：1998-08-01 00:00:00
abstract：:An in vitro perifusion system was used to investigate immunoreactive beta-endorphin (beta-END-I) release from adult human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol (HAL). Administration of a 1 microM pulse of DA consistently elicited a mean (+/- SE) 88 +/- 9% increase (p less ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000124725
更新日期：1987-03-01 00:00:00
abstract：:Previous studies have shown that neonatal administration of monosodium glutamate (MSG) results in a clearly defined lesion of the arcuate nucleus which disrupts mechanisms regulating normal FSH but not LH secretion in the adult female hamster. The present study was designed to investigate the effects of neonatally adm...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000123296
更新日期：1982-03-01 00:00:00
abstract：:In pituitary cells, c-fos transcription induced by releasing hormones and growth factors results from enhanced initiation of transcription, and sustained elongation of transcripts beyond the first intron. We studied the regulatory role of the first intron of the mouse c-fos gene for the control of its transcription in...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000054606
更新日期：2000-12-01 00:00:00
abstract：:Studies were conducted to determine if the hypothermic effects of barbiturates were responsible for their ability to suppress luteinizing hormone (LH) secretion in rats following ovariectomy or treatment with gonadal steroids. In both ovariectomized rats and rats treated with estradiol and progesterone, pentobarbital ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000124822
更新日期：1987-09-01 00:00:00
abstract：:Previous studies have indicated that 30 min of swimming in room temperature water is a potent stimulus for the secretion of beta-endorphin (beta E) from the intermediate lobe (IL) of the pituitary in rodents. Repeated daily challenge with this paradigm over days to weeks leads to a progressive increase in proopiomelan...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126553
更新日期：1993-09-01 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：:The effect of aging on the release of gonadotropin-releasing hormone (GnRH) in vitro and of luteinizing hormone (LH) both in vivo and in vitro in ovariectomized (Ovx) rats was studied. Old (21-24 months) and young (3-4 months) rats were Ovx before use. They were injected subcutaneously with estradiol benzoate (25 micr...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000125562
更新日期：1990-08-01 00:00:00
abstract：BACKGROUND:Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for thei...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000508376
更新日期：2020-05-04 00:00:00
abstract：BACKGROUND:Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM:To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS:A retrospective, multicenter, national study of C...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000512161
更新日期：2020-10-09 00:00:00
abstract：:Previous work has demonstrated that physiological concentrations of 17beta-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), ta...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000068332
更新日期：2003-01-01 00:00:00
abstract：:In this study, radiolabeled recombinant rat interleukin-1 beta (r125I-IL-1 beta) was used to localize and characterize IL-1 beta binding in rat hypothalamus and pituitary gland by quantitative autoradiography. The ability of this ligand to bind to type I IL-1 receptor was first tested on murine lymphoma cells (EL-4). ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000127026
更新日期：1995-10-01 00:00:00
abstract：:Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors were characterized and their function investigated in mouse pituitary neurointermediate lobe explants. We show that mouse neurointermediate lobes can be maintained for up to 1 month in defined medium. After 8 days in culture, these explants are devoi...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000127091
更新日期：1996-07-01 00:00:00
abstract：:We have previously shown that the serotonergic regulation of renin secretion from the kidneys is mediated by a renin-releasing factor (RRF) that is present in both plasma and hypothalamus. The present studies were designed to determine the distribution of RRF in the brain and peripheral tissues and to test whether RRF...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000126170
更新日期：1992-05-01 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：:The polyphenol curcumin (diferuloylmethane) is the active componenet of the spice plant Curcuma longa and has been shown to exert multiple actions on mammalian cells. We have studied its effect on folliculostellate (FS) TtT/GF mouse pituitary cells, representative of a multifunctional, endocrine inactive cell type of ...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000287236
更新日期：2010-01-01 00:00:00
abstract：:The aim of this study was to verify whether prolonged exposure of cultured rat anterior pituitary cells to high glucose can alter growth hormone (GH) release and responsiveness to secretagogues. Therefore, we cultured anterior pituitary cells obtained from normal male Sprague-Dawley rats in presence of normal (6 mM) o...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000125947
更新日期：1991-11-01 00:00:00
abstract：:Grafts of normal mouse preoptic area (POA) tissue into the third ventricle of gonadotrophin-releasing hormone (GnRH)-deficient hypogonadal (hpg) mice resulted in an elevation of pituitary GnRH receptors, an increased synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the pituitary gland, a...
journal_title：Neuroendocrinology
pub_type： 杂志文章
doi：10.1159/000124762
更新日期：1987-05-01 00:00:00
