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Cell Loss and Autophagy in the Extra‐Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling
Author(s) -
Schober Andreas,
Parlato Rosanna,
Huber Katrin,
Kinscherf Ralf,
Hartleben Björn,
Huber Tobias B.,
Schütz Günther,
Unsicker Klaus
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2012.02367.x
Subject(s) - atg5 , autophagy , medicine , endocrinology , biology , chromaffin cell , glucocorticoid , cathepsin d , vacuole , microbiology and biotechnology , adrenal medulla , catecholamine , apoptosis , cytoplasm , enzyme , genetics , biochemistry
Neuroendocrine chromaffin cells exist in both intra‐ and extra‐adrenal locations; the organ of Z uckerkandl ( 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 ; DBHC re 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 BM 8. 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.