Abstract:
:Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin action is mediated by the interaction with a receptor that is alternatively spliced, resulting in at least five different isoforms. The long form (OB-Rb) has a long intracellular domain that is essential for intracellular signal transduction. The specific aim of this study was to further investigate the role that the brain may play in the pathogenesis of obesity in humans. We studied the expression of OB-R mRNA (both short or common and long isoforms) in the brains of obese, lean and diabetic subjects, by in situ hybridization, semiquantitative RT-PCR and Northern blots analysis. We used two alternative probes: one that recognizes all known splice variants (OB-Ra) and a second that recognizes only the long form, OB-Rb. Several brain regions, including hypothalamus, cerebellum, neocortex, entorrhinal cortex, amygdala, and rostral medulla, were evaluated. In situ hybridization studies revealed that both OB-Ra and OB-Rb mRNAs are widely distributed in the human brain. The specific hybridization signal with both probes was detected exclusively in the cytoplasm of the cell body, dendrites and proximal axons of neurons. Hypothalamic nuclei, Purkinje cells and dentate nuclei of the cerebellum, inferior olivary and cranial nerves nuclei in the medulla, amygdala and neurons from both neocortex and entorrhinal cortex demonstrated positive signals. The hybridization signal obtained in ependyma was lower than that in neurons and no specific hybridization was detected in glial cells. No significant differences were identified among the regions or among the three groups studied. These results match those previously obtained by us [Couce et al.: Neuroendocrinology 1997;66:145] in which the distribution of the OB-R protein in the human brain was first described. RT-PCR indicated that the OB-Rb was highly expressed in the hypothalamus and cerebellum. No significant differences of OB-Ra or OB-Rb mRNA expression were identified in lean or obese individuals in these two cerebral regions. The levels of OB-Rb were significantly higher in cerebellum compared to hypothalamus in lean and obese individuals. The original hypothesis that OB-Rb is present only in the hypothalamus needs to be reconsidered. This OB-Rb isoform seems to be widely expressed in the human brain with highest levels in the cerebellum. Obesity and hyperleptinemia appears not to be associated with down-regulation of the OB-Rb in the human brain.
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
Burguera B,Couce ME,Long J,Lamsam J,Laakso K,Jensen MD,Parisi JE,Lloyd RVdoi
10.1159/000054536subject
Has Abstractpub_date
2000-03-01 00:00:00pages
187-95issue
3eissn
0028-3835issn
1423-0194pii
54536journal_volume
71pub_type
杂志文章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::We have investigated the effects of hyperprolactinemia, produced by pituitary isografts under the kidney capsule (16-20 days), on the LH releasing action and priming effect of LH-releasing hormone (LHRH) in normal and hypogonadal (hpg) female mice. The pituitary grafts increased the plasma prolactin concentrations abo...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000124585
更新日期:1986-01-01 00:00:00
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::In addition to its traditional role as a circulating vasoactive peptide, vasopressin (VP) has been shown to play significant roles in central cardiovascular processing. The recent description of VP receptors within the subfornical organ (SFO) has suggested this circumventricular organ (CVO) as a potential locus for fe...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000127230
更新日期:1997-08-01 00:00:00
abstract::Interleukin (IL)-6 in the hypothalamus and hindbrain is an important downstream mediator of suppression of body weight and food intake by glucagon-like peptide-1 (GLP-1) receptor stimulation. CNS GLP-1 is produced almost exclusively in prepro-glucagon neurons in the nucleus of the solitary tract. These neurons innerva...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000499693
更新日期:2019-01-01 00:00:00
abstract::alpha-Methyl-p-tyrosine (alpha-MT), a competitive inhibitor of tyrosine hydroxylase, was used to block the synthesis of hypothalamic catecholamines in immature female rats of 14, 16 and 30 days of age and in castrated adults. The administration of alpha-MT (300 mg/kg body weight, free base) induced a significant decay...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125611
更新日期:1990-10-01 00:00:00
abstract::Serum prolactin was measured in lightly etherized rats between 4 and 5 a.m. and between 11 a.m. and 12 noon at various times after operation in intact rats and rats that had been operated on. Serum prolactin was elevated in the late nocturnal samples from intact rats and this elevation was prevented by pinealectomy. W...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122372
更新日期:1975-01-01 00:00:00
abstract::Previous work in many laboratories has shown that luteinizing hormone-releasing hormone (LHRH) neurons display a range of shapes from smooth-contoured to extremely irregular or 'thorny'. To determine if these forms reflect or can be modified by the gonadal steroid milieu, the morphology of LHRH neurons was examined in...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125138
更新日期:1989-04-01 00:00:00
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journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000381061
更新日期:2015-01-01 00:00:00
abstract::Experiments were carried out to increase the endogenous levels of TRH in brain and spinal cord. After 7 days of continuous oral ingestion of TRH analogs (D-pGlu-Leu-ProNH2, pGlu-Leu-Pro, pGlu-Pro-ProNH2, or pGlu-Leu-pyrrolidide), spinal cord and brain levels of TRH were elevated, whereas the content of TRH metabolite,...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125118
更新日期:1989-02-01 00:00:00
abstract::The concentrations in plasma of the biologically active endogenous peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) have not been measured during development or in female rats. By radioimmunoassay, we found that Tyr-MIF-1-like immunoreactivity (Tyr-MIF-1-LI) was first consistently detectable in plasma when the rat was 5 days o...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126322
更新日期:1992-12-01 00:00:00
abstract::The sheep exhibits a marked sex difference in the timing of the pubertal increase in luteinizing hormone (LH). Male lambs undergo a reduction in sensitivity to inhibitory steroid feedback, leading to an increase in LH by 10 weeks of age, but females remain hypersensitive until 30 weeks of age. Endogenous opioids suppr...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126312
更新日期:1992-12-01 00:00:00
abstract::The push-pull perfusion technique, in conjunction with specific radioimmunoassays, was used to monitor the release of both arginine vasopressin (AVP) and oxytocin (OXT) within distinct limbic brain areas of conscious female rats. In pregnant rats near term, the release of AVP was greater than that of virgin rats in bo...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125917
更新日期:1991-10-01 00:00:00
abstract::The hypophysial portal vessels and anterior pituitary glands of adult male rats were surgically exposed, cannulated and infused for 1 min with saline, growth hormone-releasing factor (GH-RF), and dbcAMP. After cessation of infusion, anterior pituitary glands were collected at 1, 5, 15, 30 or 60 min for electron micros...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122421
更新日期:1975-01-01 00:00:00
abstract::Vasostatin, a fragment of calreticulin, was transfected in the BON cell line to evaluate the feasibility of using it for gene therapy in neuroendocrine tumors. Vasostatin transfected cells were subcutaneously inoculated in nude mice. Burkitt lymphoma cell line, CA46, colorectal adenocarcinoma cell line, SW480, as well...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000089749
更新日期:2005-01-01 00:00:00
abstract::Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) hum...
journal_title:Neuroendocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1159/000126579
更新日期:1993-10-01 00:00:00
abstract::Visual average evoked responses (AERs) to 4 intensities of light were studied in 5 patients with adrenal cortical insufficiency. Patients were tested off all medications, on ACTH while off all medications, and during replacement with carbohydrate-active steroids. Off treatment, when steroid levels were low, AERs were ...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000122452
更新日期:1975-01-01 00:00:00
abstract::Brain angiotensin II (AII) receptors play a role in the regulation of luteinizing hormone release. This action is thought to involve luteinizing hormone-releasing hormone containing neurons in the preoptic-anterior hypothalamic (POAH) area of the brain. Previous studies have demonstrated a discrete locus of AII recept...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126225
更新日期:1992-08-01 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::In 2016, the third version of guidelines for the diagnosis and treatment of neuroendocrine tumors (NETs) has been published by the European Neuroendocrine Tumor Society (ENETS). These guidelines reflect the progress in treatment of NETs, and by comparing the newest guidelines with the first guidelines of 2001, this pr...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000486096
更新日期:2018-01-01 00:00:00
abstract::Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of admi...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054583
更新日期:2000-09-01 00:00:00
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 com...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000330616
更新日期:2012-01-01 00:00:00
abstract::The effect of the antidiarrheal drug loperamide, a mu-opiate agonist, on ACTH secretion and biosynthesis, cAMP generation and phosphoinositide turnover was studied in rat anterior pituitary cell cultures. The cAMP-dependent protein kinase A pathway was stimulated with both corticotropin-releasing hormone (CRH; 2-5 nM)...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126466
更新日期:1993-06-01 00:00:00
abstract::The study was designed to determine whether the ability of central oxytocin (OT) to stimulate gonadotropin-releasing hormone (GnRH) on the afternoon of proestrus (PE) in the cycling female rat is mediated at the level of GnRH terminals within the median eminence (ME), or at higher hypothalamic levels where GnRH cell b...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054678
更新日期:2001-08-01 00:00:00
abstract::To examine the role of excitatory amino acid neurotransmitters in the regulation of LH and FSH secretion in ovariectomized (ovx) adult rats treated with estradiol and progesterone, we measured the release rates of the excitatory amino acid neurotransmitters, glutamate and aspartate, as well as the neurally inactive am...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000126673
更新日期:1994-04-01 00:00:00
abstract::The primary treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs) is surgery with curative intent or debulking of the tumor mass. In case of metastatic disease, cytoreductive options are limited. A relatively new therapeutic modality, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatos...
journal_title:Neuroendocrinology
pub_type: 杂志文章,评审
doi:10.1159/000335018
更新日期:2013-01-01 00:00:00
abstract::The response of folliculo-stellate (FS) cells of the anterior pituitary to estrogen has been studied in two strains of rat which differ in estrogen responsiveness. Fischer 344 (F344) rats are highly estrogen-responsive in comparison to Sprague-Dawley (S-D) rats. Ovariectomized adults were implanted with silastic capsu...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000125064
更新日期:1988-11-01 00:00:00
abstract::The hypothalamic GnRH pulse generator activity, which was assessed by the characteristic increases in the multiple unit activity (MUA) specifically associated with the pulsatile LH secretion (MUA volleys), was monitored throughout the estrous cycle of the female goat. Blood samples were collected daily for analysis of...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000127051
更新日期:1995-12-01 00:00:00
abstract::Somatotropes and GC cells, a GH-producing cell line, exhibit [Ca(2+)](i) oscillations that result from rhythmic Ca(2+) action potentials. Determination of this operating mode required simultaneous recording of both parameters by fura-2 imaging and patch-clamp techniques. In order to test whether patch recording induce...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000054495
更新日期:1999-11-01 00:00:00
abstract::Hypertension in male and aging female rodents is associated with glutamate-dependent plasticity in the hypothalamus, but existing models have failed to capture distinct transitional menopausal phases that could have a significant impact on the synaptic plasticity and emergent hypertension. In rodents, accelerated ovar...
journal_title:Neuroendocrinology
pub_type: 杂志文章
doi:10.1159/000446073
更新日期:2017-01-01 00:00:00