Cell loss and autophagy in the extra-adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling
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Cell loss and autophagy in the extra-adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling. / Schober, Andreas; Parlato, Rosanna; Huber, Katrin; Kinscherf, Ralf; Hartleben, Björn; Huber, Tobias B; Schütz, Günther; Unsicker, Klaus.
in: J NEUROENDOCRINOL, Jahrgang 25, Nr. 1, 01.2013, S. 34-47.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Cell loss and autophagy in the extra-adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling
AU - Schober, Andreas
AU - Parlato, Rosanna
AU - Huber, Katrin
AU - Kinscherf, Ralf
AU - Hartleben, Björn
AU - Huber, Tobias B
AU - Schütz, Günther
AU - Unsicker, Klaus
N1 - © 2012 British Society for Neuroendocrinology.
PY - 2013/1
Y1 - 2013/1
N2 - Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified. Using mice with a conditional deletion of the GC-receptor (GR) gene restricted to cells expressing the dopamine β-hydroxylase (DBH) gene [GR(fl/fl) ; DBHCre abbreviated (GR(DBHCre) )], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GR(DBHCre) mice are doubled compared to wild-type littermates. We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy. Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells. Autophagy in OZ extra-adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene (Atg5(DBHCre) mice). Cathepsin-D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8. Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GR(DBHCre) mice than in wild-type littermates. In summary, our results indicate that extra-adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling.
AB - Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified. Using mice with a conditional deletion of the GC-receptor (GR) gene restricted to cells expressing the dopamine β-hydroxylase (DBH) gene [GR(fl/fl) ; DBHCre abbreviated (GR(DBHCre) )], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GR(DBHCre) mice are doubled compared to wild-type littermates. We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy. Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells. Autophagy in OZ extra-adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene (Atg5(DBHCre) mice). Cathepsin-D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8. Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GR(DBHCre) mice than in wild-type littermates. In summary, our results indicate that extra-adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling.
KW - Animals
KW - Autophagy
KW - Caspase 3
KW - Cathepsin D
KW - Cell Count
KW - Chromaffin Cells
KW - Gene Knockdown Techniques
KW - Glucocorticoids
KW - Mice
KW - Para-Aortic Bodies
KW - Receptors, Glucocorticoid
KW - Signal Transduction
KW - Transcription Factors
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1111/j.1365-2826.2012.02367.x
DO - 10.1111/j.1365-2826.2012.02367.x
M3 - SCORING: Journal article
C2 - 23078542
VL - 25
SP - 34
EP - 47
JO - J NEUROENDOCRINOL
JF - J NEUROENDOCRINOL
SN - 0953-8194
IS - 1
ER -
