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Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Related Experiment Video

Updated: Jul 5, 2026

Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
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Published on: August 4, 2023

Leptin-dependent STAT3 phosphorylation in postnatal mouse hypothalamus.

Andrea Frontini1, Paola Bertolotti, Cristina Tonello

  • 1Institute of Normal Human Morphology, Marche Polytechnic University, Via Tronto 10/A, 60020 Ancona, Italy.

Brain Research
|May 20, 2008
PubMed
Summary

Leptin signaling in the neonatal mouse hypothalamus matures gradually, with neuronal responsiveness appearing before full differentiation. This early leptin activation precedes the reduction in feeding behavior observed in adults.

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Area of Science:

  • Neuroendocrinology
  • Developmental Neuroscience
  • Signal Transduction

Background:

  • Leptin, a hormone from adipose tissue, regulates appetite and energy expenditure in adults via the JAK2-STAT3 pathway in hypothalamic neurons.
  • Leptin levels rise early in postnatal life, peaking around postnatal day 10.

Purpose of the Study:

  • To investigate the developmental timing of leptin signal transduction system maturation in the neonatal mouse hypothalamus.
  • To identify the specific hypothalamic nuclei and cell types responsive to leptin during early development.

Main Methods:

  • Administration of intraperitoneal leptin to neonatal mice.
  • Immunohistochemical analysis for phospho-STAT3-positive cells in various hypothalamic regions.
  • Western blotting to assess STAT3 activation.
  • Double-labeling immunohistochemistry using neuronal and glial markers.

Main Results:

  • Leptin responsiveness, indicated by phospho-STAT3, was first detected in the arcuate nucleus at postnatal day 1 and became evident by day 5.
  • Responsiveness expanded to other hypothalamic areas from postnatal day 7 to 11, reaching adult-like levels by postnatal day 13.
  • Leptin-induced STAT3 activation was observed by Western blotting at postnatal days 11 and 15, comparable to adult levels, yet feeding reduction occurred later.
  • Leptin-stimulated cells were identified as neurons, but responsiveness preceded neuronal marker expression, suggesting incomplete differentiation.
  • A transient population of non-neuronal/glial cells in the third ventricle showed increased leptin-induced P-STAT3 and c-Fos, with ultrastructural features of differentiating cells.

Conclusions:

  • The leptin signaling pathway in the mouse hypothalamus matures progressively during the early postnatal period.
  • Leptin responsiveness in hypothalamic neurons precedes their full differentiation, indicating a critical developmental window.
  • A distinct, transient cell population responds to leptin, suggesting a potential role in early development not yet fully characterized.