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Published March 1992 | public
Journal Article

Changes in Competence Determine the Timing of Two Sequential Glucocorticoid Effects on Sympathoadrenal Progenitors


We have studied the control of adrenal chromaffin cell development by glucocorticoids (GCs), in a reconstituted in vitro system. The development of the chromaffin phenotype involves two sequential, GC-dependent events: the decision not to become a sympathetic neuron, and the decision to express the epinephrine-synthesizing enzyme, phenylethanolamine-N-methyltransferase (PNMT). Both decisions appear to be mediated by the type II GC receptor. Competence to express PNMT develops on a schedule in vitro which parallels that seen in vivo, but only in progenitors that have first failed to undergo neuronal differentiation. The schedule of PNMT induction is thus controlled by the time of appearance of neither the inducing signal nor its receptor, as previously suggested, but rather by a cell-intrinsic timed process in chromaffin precursors. The two effects of GCs are pharmacologically distinct, suggesting that the GC receptor may interact differently with different genes in the same cell, in a manner that changes with development.

Additional Information

© 1992 by Cell Press. Received 3 December 1991, Revised 3 January 1992. We thank Dr. Martha Bohn for providing anti-PNMT antibodies and advice on staining procedures, Liching Lo for producing the SA-1 ascites, Adela Augsburger for preparation of culture media, and members of the Anderson lab for helpful discussions. We thanks Drs. Mark Konishi, Paul Patterson, Ellen Rothenberg, Barbara Wold, and Allison Doupe for their comments on an earlier version of this manuscript. This work was supported by NIH grant NS23476 to D. j. A. and a Sloan Faculty Fellowship in Neurosciences. D. J. A. is an Assistant Investigator of the Howard Hughes Medical Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.

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October 20, 2023