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BDNF Regulates Pituitary Stem Cell Engagement towards precursor state.
Kevin Sochodolsky1, Konstantin Khetchoumian1, Aurelio Balsalobre1
1Laboratoire de génétique moléculaire, Institut de recherches cliniques de Montréal (IRCM), 110 Avenue des Pins Ouest, Montréal QC, H2W 1R7 Canada.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Pituitary stem cells differentiate into corticotrope precursors, regulated by brain-derived neurotrophic factor (BDNF) and repressed by glucocorticoids. These precursors form a signaling hub crucial for maintaining pituitary-adrenal homeostasis.
Area of Science:
- Endocrinology
- Stem Cell Biology
- Neuroscience
Background:
- Tissue stem cells differentiate through transient precursor states.
- The role of lineage precursors in tissue development is not fully understood.
- Corticotrope lineage precursors, vital for stress response, are difficult to characterize.
Purpose of the Study:
- To characterize pituitary corticotrope precursors in mouse models with deficient feedback regulation.
- To identify signals regulating corticotrope precursor differentiation and function.
- To elucidate the role of corticotrope precursors in maintaining pituitary-adrenal homeostasis.
Main Methods:
- Utilized POMC knockout and adrenalectomized mouse models.
- Investigated the role of the transcription factor Tpit in pre-corticotrope differentiation.
- Identified brain-derived neurotrophic factor (BDNF) as a key signaling molecule.
Main Results:
- Pre-corticotrope differentiation is dependent on Tpit and repressed by glucocorticoids.
- BDNF acts as a signal engaging pituitary stem cells towards differentiation.
- A glucocorticoid-sensitive BDNF autocrine loop establishes corticotrope precursors as signaling hubs.
Conclusions:
- Corticotrope precursors are critical for pituitary-adrenal homeostasis.
- BDNF is a key regulator of pituitary stem cell differentiation and tissue development.
- Understanding precursor cell dynamics is essential for tissue regulation and function.
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