title: Conditional inactivation of glucocorticoid receptor gene in dopamine-beta-hydroxylase cells impairs chromaffin cell survival.
abstract: Glucocorticoid hormones (GCs) have been thought to determine the fate of chromaffin cells from sympathoadrenal progenitor cells. The analysis of mice carrying a germ line deletion of the glucocorticoid receptor (GR) gene has challenged these previous results because the embryonic development of adrenal chromaffin cells is largely unaltered. In the present study, we have analyzed the role of GC-dependent signaling in the postnatal development of adrenal chromaffin cells by conditional inactivation of the GR gene in cells expressing dopamine-beta-hydroxylase, an enzyme required for the synthesis of noradrenaline and adrenaline. These mutant mice are viable, allowing to study whether in the absence of GC signaling further development of the adrenal medulla is affected. Our analysis shows that the loss of GR leads not only to the loss of phenylethanolamine-N-methyl-transferase expression and, therefore, to inhibition of adrenaline synthesis, but also to a dramatic reduction in the number of adrenal chromaffin cells. We provide evidence that increased apoptotic cell death is the main consequence of GR loss. These findings define the essential role of GCs for survival of chromaffin cells and underscore the specific requirement of GCs for adrenergic chromaffin cell differentiation and maintenance.
authors.affiliation: Department of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parlato
authors.forename: Christiane
authors.initials: C
authors.lastname: Otto
authors.forename: Jan
authors.initials: J
authors.lastname: Tuckermann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Stotz
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kaden
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Klaus
authors.initials: K
authors.lastname: Unsicker
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology* / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000502:physiology*
chemical_list: D011965:Receptors, Glucocorticoid; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase