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Lloyd, Ricardo V.; Jin, Long; Tsumanuma, Itaru; Vidal, Sergio; Kovács, Kálmán; Horváth, Éva; Scheithauer, Bernd W.; Couce, Marta; Burguera, Bartolomé

doi:10.1023/a:1012982626401

Cited by 66 publications

(26 citation statements)

References 150 publications

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“…2). Previous studies have indicated that STAT3 activation through tyrosine phosphorylation plays an important role in leptin signal transduction at the pituitary gland (Tsumanuma et al 2000, Lloyd et al 2001. Although pituitary cells other than thyrotropes also express leptin receptors (Sone et al 2001), our findings suggest that reduced leptin signalling in the whole pituitary gland might contribute to the abolishment of the direct effect of leptin on TSH secretion from the isolated pituitaries of the hypothyroid rats that were previously studied (Da Veiga et al 2004).…”

Section: Discussionmentioning

confidence: 52%

Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

Calvino¹,

Souza²,

Costa-e-Sousa³

et al. 2012

Journal of Endocrinology

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Leptin has been shown to regulate the hypothalamuspituitary-thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the longchain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0 . 03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 mg/100 g body weight /5 days) rats.Hypothyroid rats exhibited decreased ObRb and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3 (P!0 . 05). Except for a modest decrease in pituitary STAT3, no other alterations were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the hypothyroid rats did not exhibit a reduction in food ingestion after a single injection of leptin (0 . 5 mg/kg body weight). Therefore, hypothyroidism decreased ObRb-STAT3 signalling in the hypothalamus and pituitary gland, which likely contributes to the loss of leptin action on food intake and TSH secretion, as previously observed in hypothyroid rats.

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Section: Discussionmentioning

confidence: 52%

Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

Calvino¹,

Souza²,

Costa-e-Sousa³

et al. 2012

Journal of Endocrinology

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“…This proved to be correct for rat and human pituitary and brain and several groups confirmed and extended these findings [17, 18, 19]. High levels of leptin mRNA were also found in a human neuroblastoma cell line [20].…”

Section: Introductionmentioning

confidence: 66%

Hypothalamic Resistin Immunoreactivity Is Reduced b y Obesity in the Mouse: Co-Localization with α-Melanostimulating Hormone

Wilkinson¹,

Wilkinson²,

Wiesner

et al. 2005

Neuroendocrinology

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Resistin is a new adipokine expressed in mouse, rat and human adipose tissue. Resistin may be an important link between obesity and insulin resistance, though this controversial view is complicated by the discovery of multiple sites of resistin expression, including human macrophages, placenta and pancreas. In previous studies we demonstrated that the mouse hypothalamo-pituitary system was also a site of resistin production. Pituitary resistin is developmentally regulated, reduced in the ob/ob mouse and severely down-regulated by food deprivation (24 h). An unexpected finding was that hypothalamic resistin mRNA remained unaffected by fasting. The present experiments examined the localization and possible regulation of hypothalamic resistin protein. Using immunohistochemistry we observed a complex network of resistin+ fibres extending rostrally from the arcuate nucleus of the hypothalamus (ARC) to the preoptic area. Labelled cell bodies occurred only in the ARC and in a periventricular region of the dorsal hypothalamus. Hypothalamic resistin immunoreactivity (ir) was unaffected by fasting (48 h) or by a high fat diet, but the periventricular staining was greatly increased in the lactating mouse. Marked reductions in resistin+ fibres were seen in brain tissue from: (a) ob/ob mice, (b) young mice made underweight for their age by raising them in large litters (20 pups per litter) and (c) mice with hypothalamic lesions induced by monosodium glutamate (MSG) or gold thioglucose (GTG). We speculate that the resistin-ir deficit in genetically obese mice, and in severely underweight mice, could be due to low or absent leptin. In contrast, though MSG- and GTG-treated mice have high levels of circulating leptin, in the presence of excessive visceral fat deposits, we hypothesize that damage to the ARC destroys the resistin+ cell bodies. This latter supposition led us to an additional hypothesis, that resistin-ir would be contained in neurons expressing the proopiomelanocortin (POMC) gene. This proved to be correct. Double label immunofluorescence histochemistry revealed that α-MSH-ir, a marker for POMC neurons, was co-localized with resistin-ir. In conclusion, our data reveal a second example of an adipocytokine co-localized with a hypothalamic neuropeptide. We reported previously that leptin was co-localized with oxytocin and vasopressin. RT-PCR analysis confirmed that resistin mRNA is readily detectable in ARC, but further work is required to determine whether the resistin gene is expressed in POMC neurons or if resistin is specifically accumulated by these cells. Nonetheless, our data suggest that the hypothalamus is a target tissue for resistin.

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“…It has been speculated that leptin and GH directly interact (28,31). Some of the GH cells in the pituitary contain leptin granules and have leptin receptors (31,47). Moreover, homozygous mutations of the leptin receptor gene lead to decreased GH secretion (47).…”

Section: Discussionmentioning

confidence: 99%

“…Pituitary radiation and pituitary surgery itself may change hypothalamic ghrelin and leptin sensitivity as the GH secretagogue receptor (GHSR) on which ghrelin binds is also located in the hypothalamus (48), and leptin granules and receptors were detected in GH cells of the pituitary (31,47). …”

Section: Discussionmentioning

confidence: 99%

Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients

Roemmler¹,

Otto²,

Arafat³

et al. 2010

European Journal of Endocrinology

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Introduction: Pegvisomant (peg) is a GH receptor antagonist. In de novo acromegalic patients with high GH levels, ghrelin and leptin levels are reduced, suggesting a direct GH-mediated effect. The aim of our study was to evaluate whether peg treatment in acromegalic patients may abolish the GH impact on ghrelin and leptin levels. Methods: Ghrelin, leptin and endogenous GH were measured in ten peg-treated acromegalic patients (three females/seven males, 47 years (28-57)), ten patients with active (act) and ten patients with inactive disease (inact) as well as in ten gender-, age-and body mass index (BMI)-matched healthy volunteers (controls). Endogenous GH was measured using a special in-house assay without interference by peg; total ghrelin and leptin were determined using a commercial RIA and an immunofluorometric in-house assay respectively. Results: Age and BMI did not differ significantly between groups. Endogenous GH was significantly higher in peg (6.3 mg/l (1.5-41)) and act (9.3 mg/l (1.7-70)) compared with controls (0.1 mg/l (0.1-3.1)) and inact (0.35 mg/l (0.1-2.0), P!0.001). Ghrelin was significantly higher in peg (232 ng/l (96-351)) compared with act (102 ng/l (33-232), P!0.01), whereas ghrelin was not significantly different between the other groups. Leptin was highest in controls (19 mg/l (4-57)) and lowest in act (6 mg/l (2-21)), but this difference did not reach significance. Conclusion: Treatment with peg seems to disrupt the feedback loop of ghrelin and GH, leading to elevated ghrelin levels. Furthermore, peg therapy appears not to have a strong impact on leptin levels, as acromegalic patients with and without peg treatment showed similar leptin levels.

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Cited by 66 publications

References 150 publications

Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action

Hypothalamic Resistin Immunoreactivity Is Reduced b y Obesity in the Mouse: Co-Localization with α-Melanostimulating Hormone

Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients

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