{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:58:22Z","timestamp":1791305902232,"version":"4.3.1"},"reference-count":56,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:p>The adrenal androgen dehydroepiandrosterone (DHEA) is produced in the inner zone of the adrenal cortex, which is in direct contact to adrenal medullary cells. Due to their close anatomical proximity and tightly intermingled cell borders, a direct interaction of adrenal cortex and medulla has been postulated. In humans congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in androgen excess accompanied by severe adrenomedullary dysplasia and chromaffin cell dysfunction. Therefore, to define the mechanisms of DHEA action on chromaffin cell function, we investigated its effect on cell survival and differentiation processes on a molecular level in the chromaffin cell line PC12. DHEA lessened the positive effect of NGF on cell survival and neuronal differentiation. Nerve growth factor (NGF)-mediated induction of a neuronal phenotype was inhibited by DHEA as indicated by reduced neurite outgrowth and decreased expression of neuronal marker proteins such as synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein-2. We examined whether DHEA may stimulate the cells toward a neuroendocrine phenotype. DHEA significantly elevated catecholamine release from unstimulated PC12 cells in the presence but not absence of NGF. Accordingly, DHEA enhanced the expression of the neuroendocrine marker protein chromogranin A. Next, we explored the possible molecular mechanisms of DHEA and NGF interaction. We demonstrate that NGF-induced ERK1\/2 phosphorylation was reduced by DHEA. In summary, our data show that DHEA influences cell survival and differentiation processes in PC12 cells, possibly by interacting with the ERK1\/2 MAPK pathway. DHEA drives NGF-stimulated cells toward a neuroendocrine phenotype, suggesting that the interaction of intraadrenal steroids and growth factors is required for the maintenance of an intact adrenal medulla.<\/jats:p>","DOI":"10.1210\/en.2007-0645","type":"journal-article","created":{"date-parts":[[2007,9,21]],"date-time":"2007-09-21T00:48:56Z","timestamp":1190335736000},"page":"320-328","source":"Crossref","is-referenced-by-count":25,"title":["Dehydroepiandrosterone Induces a Neuroendocrine Phenotype in Nerve Growth Factor-Stimulated Chromaffin Pheochromocytoma PC12 Cells"],"prefix":"10.1210","volume":"149","author":[{"given":"Christian G.","family":"Ziegler","sequence":"first","affiliation":[{"name":"Medical Clinic III (C.G.Z., F.S., S.R.B., M.E.-B., A.W.K.), Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Sicard","sequence":"first","affiliation":[{"name":"Medical Clinic III (C.G.Z., F.S., S.R.B., M.E.-B., A.W.K.), Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lattke","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine (P.L.), Carl Gustav Carus University Hospital, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan R.","family":"Bornstein","sequence":"first","affiliation":[{"name":"Medical Clinic III (C.G.Z., F.S., S.R.B., M.E.-B., A.W.K.), Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Ehrhart-Bornstein","sequence":"first","affiliation":[{"name":"Medical Clinic III (C.G.Z., F.S., S.R.B., M.E.-B., A.W.K.), Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W.","family":"Krug","sequence":"first","affiliation":[{"name":"Medical Clinic III (C.G.Z., F.S., S.R.B., M.E.-B., A.W.K.), Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2007,9,20]]},"reference":[{"key":"2020071612320174700_R1","first-page":"225","article-title":"Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions.","volume":"78","author":"Bornstein","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612320174700_R2","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1210\/en.2005-0263","article-title":"Dehydroepiandrosterone sulfate and allopregnanolone directly stimulate catecholamine production via induction of tyrosine hydroxylase and secretion by affecting actin polymerization.","volume":"146","author":"Charalampopoulos","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612320174700_R3","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1055\/s-2005-870307","article-title":"Intranasal administration of ACTH (1\u201324) stimulates catecholamine secretion.","volume":"37","author":"Yoshida-Hiroi","year":"2005","journal-title":"Horm Metab Res"},{"key":"2020071612320174700_R4","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1523\/JNEUROSCI.11-11-03507.1991","article-title":"Antibody markers identify a common progenitor to sympathetic neurons and chromaffin cells in vivo and reveal the timing of commitment to neuronal differentiation in the sympathoadrenal lineage.","volume":"11","author":"Anderson","year":"1991","journal-title":"J Neurosci"},{"key":"2020071612320174700_R5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1055\/s-2007-978976","article-title":"17\u03b1-Hydroxylase and chromogranin A in 6th week human fetal adrenals.","volume":"29","author":"Ehrhart-Bornstein","year":"1997","journal-title":"Horm Metab Res"},{"key":"2020071612320174700_R6","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1096\/fasebj.13.10.1185","article-title":"Adrenomedullary function is severely impaired in 21-hydroxylase-deficient mice.","volume":"13","author":"Bornstein","year":"1999","journal-title":"FASEB J"},{"key":"2020071612320174700_R7","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1056\/NEJM200011093431903","article-title":"Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency.","volume":"343","author":"Merke","year":"2000","journal-title":"N Engl J Med"},{"key":"2020071612320174700_R8","doi-asserted-by":"crossref","first-page":"320","DOI":"10.7326\/0003-4819-136-4-200202190-00012","article-title":"NIH conference. 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