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Tsumanuma, Itaru; Jin, Long; Zhang, S; Bayliss, Jill; Scheithauer, B. W.; Lloyd, Ricardo V.

doi:10.1023/a:1012994712851

Cited by 23 publications

(6 citation statements)

References 56 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: 51%

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: 51%

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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“…The long form Ob-Rb is the active form of the receptor [56], and its mRNA is expressed in the pig pituitary [57]. Activation of the Ob-Rb results in Jak2 phosphorylation, activation of STATs and subsequent gene expression [58, 59, 60]. The short form of Ob-R (Ob-Ra) that has been generally thought to be inactive at signaling can actually induce the expression of immediate early genes [61]and transmits signals through MAP kinase [62].…”

Section: Discussionmentioning

confidence: 99%

Effects of Leptin on Intracellular Calcium Concentrations in Isolated Porcine Somatotropes

Glavaski-Joksimovic

Rowe²,

Jeftinija³

et al. 2004

Neuroendocrinology

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Leptin, the product of the obese gene, is a protein that is secreted primarily from adipocytes. Leptin can influence the function of the pituitary gland through its action on the hypothalamus, but it can also directly act at the level of the pituitary gland. The ability of leptin to induce an increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in somatotropes was examined in dispersed porcine pituitary cells using a calcium imaging system. Somatotropes were functionally identified by the application of human growth hormone releasing hormone. Leptin increased [Ca²⁺]_i in porcine somatotropes in a dose-dependent manner. The application of 100 nM leptin for 3 min did not have a significant effect on [Ca²⁺]_i, while a 3-min application of 1 µM leptin increased [Ca²⁺]_i in about 50% of the somatotropes (p < 0.01). The application of a second leptin challenge (1 µM) evoked a response in only 18% of the observed somatotropes. The stimulatory effect of leptin was abolished in low calcium saline and blocked by nifedipine, an L-calcium channel blocker, suggesting an involvement of calcium channels. Pretreatment of the cultures with AG 490, a specific Janus kinase inhibitor, and with SB 203580, a mitogen-activated protein kinase (MAP kinase) inhibitor, abolished the increase in [Ca²⁺]_ievoked by leptin. In the presence of N^ω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, the magnitude of the increase in [Ca²⁺]_i evoked by 1 µM leptin was not significantly changed. However, in the presence of L-NAME only 24% of the somatotropes responded to leptin, while in parallel control cultures 70% of the somatotropes responded to leptin. These results imply an involvement of Janus kinase/signal transducer and activator or transcription, MAP kinase and NOS-signaling pathways in the stimulatory effect of leptin on porcine somatotropes.

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“…These signals are well described in the hypothalamus and include the JAK2-STAT-3 and the PI 3 kinase pathways [69, 143]. There is also good evidence that PI 3 kinase is expressed in high abundance in the anterior pituitary [144] as is the STAT-3/SOCS-3 signaling system [145,146,147]. Leptin receptors are present in all anterior pituitary cell types [140] and we reported a homogeneous distribution of leptin receptor-ir throughout the prepubertal rat pituitary [134].…”

Section: Pituitary Adipokinesmentioning

confidence: 99%

“…There is evidence that leptin can activate the pituitary JAK-STAT pathway. Using the immortalized HP75 human pituitary cell line, Tsumanuma et al [145] reported that leptin stimulated the expression of socs-3 mRNA and phosphorylation of SOCS-3. Studies in isolated porcine somatotropes revealed that leptin increased intracellular calcium ion levels via JAK-STAT and MAPK pathways [148].…”

Section: Pituitary Adipokinesmentioning

confidence: 99%

“…Thus, increased levels of leptin in the developing pituitary could be the result of increased Pit-1 activity, pointing to a developmental role for pituitary-derived leptin. Treatment of GH3 cells, a somatomammotrope cell line, or HP75 cells, with leptin reduced cell growth and increased apoptosis [21, 145]. In contrast, leptin had no effect on the growth of LβT2 or αT 3 -1 gonadotropic cell lines [21] or folliculostellate cells [128], suggesting that leptin stimulates apoptosis in a cell-type-specific manner.…”

Section: Pituitary Adipokinesmentioning

confidence: 99%

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Adipokine Gene Expression in Brain and Pituitary Gland

Wilkinson

Brown²,

Imran³

et al. 2007

Neuroendocrinology

104

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The brain has been recognized as a prominent site of peptide biosynthesis for more than 30 years, and many neuropeptides are now known to be common to gut and brain. With these precedents in mind it is remarkable that adipose-derived peptides like leptin have attracted minimal attention as brain-derived putative neuromodulators of energy balance. This review outlines the evidence that several adipose-specific genes are also expressed in the central nervous system and pituitary gland. We, and others, confirmed that the genes for leptin, resistin, adiponectin, FIAF (fasting-induced adipose factor) and adiponutrin are expressed and regulated in these tissues. For example, leptin mRNA was readily detectable in human, rat, sheep and pig brain, but not in the mouse. Leptin expression in rat brain and pituitary was regulated through development, by food restriction, and following traumatic brain injury. In contrast, hypothalamic resistin mRNA was unaffected by age or by fasting, but was significantly depleted by food restriction in mouse pituitary gland. Similar results were seen in the ob/ob mouse, and we noted a marked reduction in resistin-positive hypothalamic nerve fibres. Resistin and fiaf mRNA were also upregulated in hypoxic/ischaemic mouse brain. Our studies on the regulation of neuronal adipokines were greatly aided by the availability of clonal hypothalamic neuronal cell lines. One of these, N-1, expresses both rstn and fiaf together with several other neuropeptides and receptors involved in energy homeostasis. Selective silencing of rstn revealed an autocrine/paracrine regulatory system, mediated through socs-3 expression that may influence the feedback effects of insulin and leptin in vivo. A similar convergence of signals in the pituitary gland could also influence anterior pituitary hormone secretion. In conclusion, the evidence is suggestive that brain and pituitary-derived adipokines represent a local regulatory circuit that may fine tune the feedback effects of adipose hormones in the control of energy balance.

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Cited by 23 publications

References 56 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

Effects of Leptin on Intracellular Calcium Concentrations in Isolated Porcine Somatotropes

Adipokine Gene Expression in Brain and Pituitary Gland

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