Dehydroepiandrosterone-sulphate (DHEA-S) promotes neuroendocrine differentiation of chromaffin pheochromocytoma PC12 cells. 2009

Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Germany. krugaw@mail.nih.gov

The major source for dehydroepiandrosterone (DHEA) and its sulphate compound DHEA-S is the inner zone of the adrenal cortex, which is in direct contact to adrenomedullary chromaffin cells. Due to their close proximity, direct interactions of DHEA and DHEA-S with chromaffin cells during adrenal gland development and throughout the whole life span are hypothesized. A possible direct effect of DHEA-S and the cellular and molecular mechanisms of DHEA-S action on chromaffin cells remain unresolved. Therefore, in this study, we aimed at clarifying DHEA-S effects and mechanisms of action on rat chromaffin PC12 cells. DHEA-S (10(-6)mol/l) inhibited nerve growth factor (NGF, 20ng/ml)-induced cell proliferation by 66% (n=4, p<0.001). In NGF-stimulated cells, neuronal differentiation was inhibited by DHEA-S, as demonstrated by a 22% reduction (n=3; p<0.05) of neuronal differentiation marker expression, synaptosome-associated protein of 25kDa (SNAP-25), and a 59% (n=6; p<0.001) decrease in neurite outgrowth. Moreover, DHEA-S stimulated expression of endocrine marker chromogranin A (CgA) by 31% (n=4; p<0.05 vs. control) and catecholamine release from NGF-treated PC12 cells by 229% (n=3-5; p<0.001), indicating a DHEA-S-induced shift towards neuroendocrine differentiation. On a molecular level, DHEA-S diminished NGF-induced ERK1/2 phosphorylation. Taken together, DHEA-S inhibited NGF-induced proliferation and neuronal differentiation and shifted cells towards a more endocrine phenotype. Interference of DHEA-S with NGF-stimulated ERK1/2 activation might be involved in this effect. Our study provides support for the notion that adrenocortical-derived DHEA-S impacts adrenomedullary chromaffin cells during development and differentiation.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D048049 Extracellular Signal-Regulated MAP Kinases A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS. ERK MAP Kinase,ERK MAP Kinases,Extracellular Signal-Regulated Kinase,Extracellular Signal-Regulated Kinases,Extracellular Signal-Regulated MAP Kinase,MAP Kinases, Extracellular Signal-Regulated,Extracellular Signal Regulated Kinase,Extracellular Signal Regulated Kinases,Extracellular Signal Regulated MAP Kinase,Extracellular Signal Regulated MAP Kinases,Kinase, ERK MAP,Kinase, Extracellular Signal-Regulated,Kinases, Extracellular Signal-Regulated,MAP Kinase, ERK,MAP Kinases, Extracellular Signal Regulated,Signal-Regulated Kinase, Extracellular
D050825 Synaptosomal-Associated Protein 25 A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES. SNAP-25 Protein,SNAP-25B Protein,SNAP25 Protein,SNAP 25 Protein,SNAP 25B Protein,Synaptosomal Associated Protein 25
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D053379 Chromogranin A A type of chromogranin which was first isolated from CHROMAFFIN CELLS of the ADRENAL MEDULLA but is also found in other tissues and in many species including human, bovine, rat, mouse, and others. It is an acidic protein with 431 to 445 amino acid residues. It contains fragments that inhibit vasoconstriction or release of hormones and neurotransmitter, while other fragments exert antimicrobial actions. CHGA Protein,Parathyroid Secretory Protein,Secretory Protein I, Parathyroid Gland,Secretory Protein, Parathyroid
D019314 Dehydroepiandrosterone Sulfate The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. DHEA Sulfate,DHA Sulfate,Dehydroisoandrosterone Sulfate,Prasterone Sulfate,Sulfate, DHA,Sulfate, DHEA,Sulfate, Dehydroepiandrosterone,Sulfate, Dehydroisoandrosterone,Sulfate, Prasterone
D020932 Nerve Growth Factor NERVE GROWTH FACTOR is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. NGF,Nerve Growth Factor 1,Nerve Growth Factor alpha Subunit,Nerve Growth Factor beta Subunit,Nerve Growth Factor gamma Subunit,NGF-1beta,beta-Nerve Growth Factor,Factor, beta-Nerve Growth,NGF 1beta,beta Nerve Growth Factor

Related Publications

Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
January 2008, Endocrinology,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
March 1995, Nihon rinsho. Japanese journal of clinical medicine,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
December 1999, Nihon rinsho. Japanese journal of clinical medicine,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
December 1999, Acta paediatrica (Oslo, Norway : 1992). Supplement,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
March 2004, The international journal of neuropsychopharmacology,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
January 1990, Chronobiologia,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
September 2010, Recenti progressi in medicina,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
April 2006, The journal of headache and pain,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
October 1991, European journal of haematology,
Alexander W Krug, and Heike Langbein, and Christian G Ziegler, and Stefan R Bornstein, and Graeme Eisenhofer, and Monika Ehrhart-Bornstein
June 2004, Polskie Archiwum Medycyny Wewnetrznej,
Copied contents to your clipboard!