Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Functional map of sst subtypes in the brain

Hypothalamic leptinoceptive neurons can be visualized by histochemical demonstration of leptin-induced nuclear translocation of the signaling molecule STAT3. We investigated the relation of the leptinoceptive neurons to the somatostatin signaling system. With double-labeling immunohistochemistry we have studied the co-localization of leptin-activated transcription factor STAT3 with somatostatin receptor subtypes sst1, sst2A, sst2B, sst3 and sst4 or the neuropeptide itself in rat hypothalamus. Immunoreactivity for all the entities was widely distributed throughout the entire hypothalamus.

Despite the wide distribution, only few cases of co-localization of somatostatin with leptin-activated STAT3 were detected in the paraventricular, arcuate and dorsomedial nuclei. A moderate to high degree of co-localization of nuclear STAT3 and all investigated subtypes of somatostatin receptors was found in the lateral and dorsal hypothalamic areas and in the dorsomedial hypothalamic nucleus. Immunoreactivity for sst1, sst2B and sst4 was present in STAT3-containing nuclei of the paraventricular, periventricular, arcuate and ventromedial hypothalamic neurons as well as in the retrochiasmatic and posterior hypothalamic areas. Despite the wide distribution of sst2A in rat hypothalamus, few events of co-localization with leptin-activated STAT3 were observed in the dorsomedial nucleus and in the lateral and dorsal hypothalamic areas only. Many leptin-responsive neurons of the dorsal, lateral, periarcuate, perifornical and posterior hypothalamic areas as well as in the ventromedial and dorsomedial hypothalamic nuclei displayed sst3 immunoreactivity at their neuronal cilia. These results provide a strong anatomical evidence for the direct interaction of leptin and the somatostatinergic system in neuroendocrine control loops such as the energy homeostasis, growth or stress response.

By detecting nuclear STAT3 translocation in rat hypothalamus we investigated the possible influence of somatostatin on leptin central action. We demonstrated that somatostatin as well as sst1, sst2 and sst3 selective agonists, administered centrally prior to leptin injection, inhibited the activation of STAT3 that is resulted in the decrease in number of STAT3 positive cells and decrease in the amount of phosphorylated STAT3 in rat hypothalamus. Furthermore, we showed that somatostatin inhibits the activation of STAT3 by leptin in dose-dependent manner.

Additionally, somatostatin and sst1, sst2 and sst3 agonists counteract the suppression of 24-hour food intake caused by leptin. In contrast, sst4 selective agonist, applied before leptin injection did not cause any change in STAT3 activation as well as in anorexia induced by leptin.

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Arthur-Scheunert-Allee 114-116
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