Glucocorticoid‐Dependent Action of Neural Crest Factor AP‐2: Stimulation of Phenylethanolamine <i>N</i>‐Methyltransferase Gene Expression

Ebert, Steven N.; Ficklin, Mary Beth; Her, Song; Siddall, Brenda; Bell, Rose Ann; Ganguly, Karunesh; Morita, Kyoji; Wong, Dona L.

doi:10.1046/j.1471-4159.1998.70062286.x

Cited by 44 publications

(40 citation statements)

References 14 publications

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“…This concurs with studies that have revealed low levels of PNMT mRNA expression in human phaeochromocytoma (Isobe et al 1998). Factors that have been shown to control PNMT expression include cortisol and glucocorticoid receptors (Isobe et al 2000;Finotto et al 1999), the immediate early gene transcription factor Egr-1 (Isobe et al 2000), neural-crest associated developmental transcription factor, AP2 (Ebert et al 1998) and pituitary adenylate cyclase-activating polypeptide (Isobe et al 2003). An alteration in any of these factors may play a role in the variable PNMT expression levels that we describe in human phaeochromocytoma.…”

Section: Discussionmentioning

confidence: 99%

Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma

et al. 2005

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Expression of the noradrenaline transporter (NAT) was examined in normal human adrenal medulla and phaeochromocytoma by using immunohistochemistry and confocal microscopy. The enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were used as catecholamine biosynthetic markers and chromogranin A (CGA) as a marker for secretory granules. Catecholamine content was measured by using high performance liquid chromatography (HPLC). In normal human adrenal medulla (n=5), all chromaffin cells demonstrated strong TH, PNMT and NAT immunoreactivity. NAT was co-localized with PNMT and was located within the cytoplasm with a punctate appearance. Human phaeochromocytomas demonstrated strong TH expression (n=20 samples tested) but variable NAT and PNMT expression (n=24). NAT immunoreactivity ranged from absent (n=3) to weak (n=10) and strong (n=11) and, in some cases, occupied an apparent nuclear location. Unlike the expression seen in normal human adrenal medullary tissue, NAT expression was not consistently co-localized with PNMT. PNMT also showed highly variable expression that was poorly correlated with tumour adrenaline content. Immunoreactivity for CGA was colocalized with NAT within the cytoplasm of normal human chromaffin cells (n=4). This co-localization was not consistent in phaeochromocytoma tumour cells (n=7). The altered pattern of expression for both NAT and PNMT in phaeochromocytoma indicates a significant disruption in the regulation and possibly in the function of these proteins in adrenal medullary tumours.

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Section: Discussionmentioning

confidence: 99%

Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma

et al. 2005

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“…1A) upstream of the firefly luciferase reporter gene (pGL3RP893) were treated with varying concentrations of NGF up to 100 ng/ml, and PNMT promoter-driven luciferase reporter gene expression was de- (Ross et al, 1990;Ebert et al, 1994Ebert et al, , 1998Ebert and Wong, 1995;Wong et al, 1998;Her et al, 1999). B, transfected cells were treated with varying doses of NGF from 0 to 100 ng/ml, and luciferase activity was determined after 24 h. C, transfected cells were treated with 50 ng/ml NGF for times up to 24 h, and luciferase activity was determined.…”

Section: Ngf Activation Of the Pnmt Promotermentioning

confidence: 99%

Nerve Growth Factor Regulates Adrenergic Expression

Tai

Wong-Faull²,

Claycomb³

et al. 2006

Mol Pharmacol

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The mechanism by which nerve growth factor (NGF) regulates adrenergic expression was examined in PC-12 cells transfected with a rat phenylethanolamine N-methyl-transferase (PNMT) promoter-luciferase reporter gene construct pGL3RP893. NGF treatment increased PNMT promoter-driven luciferase activity in a dose-and time-dependent manner. Induction was attenuated by inhibition of the extracellular signalregulated kinase mitogen-activated protein kinase (MAPK) pathway (ϳ60%) but not by inhibition of the protein kinase A (PKA), protein kinase C, phosphoinositol kinase, or p38 MAPK pathways. Deletion PNMT promoter-luciferase reporter gene constructs showed that the NGF-responsive sequences lay within the proximal Ϫ392 base pairs (bp) of PNMT promoter, wherein binding elements for Egr-1 (Ϫ165 bp) and Sp1 (Ϫ48 bp) reside. Western analysis further showed that NGF increased nuclear levels of Egr-1, but not Sp1 or the catalytic subunit of PKA. Gel mobility shift assays showed increased potential for Egr-1, but not Sp1, protein-DNA binding complex formation. Mutation of either the Egr-1 or Sp1 binding sites in the PNMT promoter attenuated NGF activation. NGF, combined with pituitary adenylyl cyclase-activating protein (PACAP), another PNMT transcriptional activator, cooperatively stimulated PNMT promoter driven-luciferase activity beyond levels observed with either neurotrophin alone. Finally, posttranscriptional control seems to be another important mechanism by which neurotrophins regulate the adrenergic phenotype. NGF, PACAP, and a combination of the two stimulated both intron-retaining and intronless PNMT mRNA and PNMT protein, but to different extents.

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“…For example, stimulation of the PNMT gene by the neural crest factor activating protein-2 (AP-2) requires a direct interaction with ligand-activated type II glucocorticoid receptors. 34 In addition, the PNMT gene contains overlapping consensus elements for the promoter selective transcription factor (Sp 1) and the immediate early gene transcription factor Egr-1 that are capable of differentially activating PNMT gene expression. 35 Sp 1, Egr-1 and the glucocorticoid receptor and AP-2 function cooperatively to stimulate PNMT promoter activity through poorly delineated mechanisms.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice

et al. 2002

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Corticotropin-releasing hormone (CRH) is both a main regulator of the hypothalamic-pituitaryadrenocortical axis and the autonomic nervous system. CRH receptor type 1 (CRHR1)-deficient mice demonstrate alterations in behavior, impaired stress responses with adrenocortical insufficiency and aberrant neuroendocrine development, but the adrenal medulla has not been analyzed in these animals. Therefore we studied the production of adrenal catecholamines, expression of the enzyme responsible for catecholamine biosynthesis neuropeptides and the ultrastructure of chromaffin cells in CRHR1 null mice. In addition we examined whether treatment of CRHR1 null mice with adrenocorticotropic hormone (ACTH) could restore function of the adrenal medulla. CRHR1 null mice received saline or ACTH, and wildtype or heterozygous mice injected with saline served as controls. Adrenal epinephrine levels in saline-treated CRHR1 null mice were 44% those of controls (P Ͻ0.001), and the phenylethanolamine N-methyltransferase (PNMT) mRNA levels in CRHR1 null mice were only 25% of controls (P Ͻ0.001). ACTH treatment increased epinephrine and PNMT mRNA level in CRHR1 null mice but failed to restore them to normal levels. Proenkephalin mRNA in both saline-and ACTH-treated CRHR1 null mice were higher than in control animals (215.8% P Ͻ0.05, 268.9% P Ͻ0.01) whereas expression of neuropeptide Y and chromogranin B did not differ. On the ultrastructural level, chromaffin cells in saline-treated CRHR1 null mice exhibited a marked depletion in epinephrine-storing secretory granules that was not completely normalized by ACTH-treatment. In conclusion, CRHR1 is required for a normal chromaffin cell structure and function and deletion of this gene is associated with a significant impairment of epinephrine biosynthesis. Molecular Psychiatry (2002) 7, 967-974.

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Glucocorticoid‐Dependent Action of Neural Crest Factor AP‐2: Stimulation of Phenylethanolamine N‐Methyltransferase Gene Expression

Cited by 44 publications

References 14 publications

Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma

Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma

Nerve Growth Factor Regulates Adrenergic Expression

Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice

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