scholarly journals Corticotropin-Releasing Factor (CRF) and the Urocortins Differentially Regulate Catecholamine Secretion in Human and Rat Adrenals, in a CRF Receptor Type-Specific Manner

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1524-1538 ◽  
Author(s):  
E. Dermitzaki ◽  
C. Tsatsanis ◽  
V. Minas ◽  
E. Chatzaki ◽  
I. Charalampopoulos ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Chromaffin Cells ◽  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
Catecholamine Secretion ◽  
Dependent Manner ◽  
Receptor System ◽  
Catecholamine Synthesis ◽  
Receptor Agonists ◽  
Rat Adrenals

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.

scholarly journals Dehydroepiandrosterone Sulfate and Allopregnanolone Directly Stimulate Catecholamine Production via Induction of Tyrosine Hydroxylase and Secretion by Affecting Actin Polymerization

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3309-3318 ◽  
Author(s):  
I. Charalampopoulos ◽  
Ε. Dermitzaki ◽  
L. Vardouli ◽  
C. Tsatsanis ◽  
C. Stournaras ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Actin Filament ◽  
Chromaffin Cells ◽  
Actin Polymerization ◽  
Dehydroepiandrosterone Sulfate ◽  
Neuroactive Steroids ◽  
Zona Reticularis ◽  
Catecholamine Synthesis ◽  
Catecholamine Levels

Abstract Adrenal cortical cells of zona reticularis produce the neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester dehydroepiandrosterone sulfate (DHEAS), and allopregnanolone (ALLO). An interaction between zona reticularis and adrenal medulla has been postulated based on their close proximity and their interwoven borders. The aim of this paper was to examine in vitro the possible paracrine effects of these steroids on catecholamine production from adrenomedullary chromaffin cells, using an established in vitro model of chromaffin cells, the PC12 rat pheochromocytoma cell line. We have found the following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10–30 min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels (norepinephrine and dopamine). 2) It appears that the acute effect of these steroids involved actin depolymerization/actin filament disassembly, a fast-response cellular system regulating trafficking of catecholamine vesicles. Specifically, 10−6m phallacidin, an actin filament stabilizer, completely prevented steroid-induced catecholamine secretion. 3) DHEAS and ALLO, but not DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased catecholamine levels at 24 h, an effect blocked by l-2-methyl-3-(-4hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of tyrosine hydroxylase and l-aromatic amino acid decarboxylase, respectively, suggesting that this effect involved catecholamine synthesis. The latter hypothesis was confirmed by finding that DHEAS and ALLO increased both the mRNA and protein levels of tyrosine hydroxylase. In conclusion, our findings suggest that neuroactive steroids exert a direct tonic effect on adrenal catecholamine synthesis and secretion. These data associate the adrenomedullary malfunction observed in old age and neuroactive steroids.

scholarly journals Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism

2005 ◽  
Vol 186 (2) ◽  
pp. R1-R5 ◽  
Author(s):  
Damien J Keating ◽  
Chen Chen
Keyword(s):  
Adrenal Cortex ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Transforming Growth Factor ◽  
Activin A ◽  
Catecholamine Secretion ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Adrenal Chromaffin Cells ◽  
Adrenal Chromaffin

Activin A is a member of the transforming growth factor-β family and has known roles in the adrenal cortex, from which activin A is secreted. We aimed to find whether activin A induces secretion of catecholamines from chromaffin cells of the adrenal medulla, which neighbours the adrenal cortex in vivo. Using carbon fibre amperometry, we were able to measure catecholamine secretion in real-time from single chromaffin cells dissociated from the rat adrenal medulla. Activin A stimulated catecholamine secretion in a rapid and dose-dependent manner from chromaffin cells. This effect was fully reversible upon washout of activin A. The minimum dose at which activin A had a maximal effect was 2 nM, with an EC50 of 1.1 nM. The degree of secretion induced by activin A (2 nM) was smaller than that due to membrane depolarization caused by an increase in the external K+ concentration from 5 to 70 mM. No response to activin A was seen when Ca2+ channels were blocked by Cd2+ (200 μM). We conclude from these findings that activin A is capable of stimulating a robust level of catecholamine secretion from adrenal chromaffin cells in a concentration-dependent manner. This occurs via the opening of voltage-gated Ca2+ channels, causing Ca2+ entry, thereby triggering exocytosis. These findings illustrate a new physiological role of activin A and a new mechanism in the control of catecholamine secretion from the adrenal medulla.

scholarly journals Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5332-5340 ◽  
Author(s):  
Yoshihiro Kano ◽  
Fumio Otsuka ◽  
Masaya Takeda ◽  
Jiro Suzuki ◽  
Kenichi Inagaki ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Pc12 Cells ◽  
Bone Morphogenetic Proteins ◽  
Bmp Signaling ◽  
Type I ◽  
Dependent Manner ◽  
Catecholamine Synthesis ◽  
Pheochromocytoma Cells ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

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