scholarly journals Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1121 ◽  
Author(s):  
Berends ◽  
Eisenhofer ◽  
Fishbein ◽  
Horst-Schrivers ◽  
Kema ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Histopathological Examination ◽  
Unmet Need ◽  
Sympathetic Ganglia ◽  
Prognostic Biomarkers ◽  
Adrenal Chromaffin Cell ◽  
Catecholamine Biosynthesis ◽  
Molecular Machinery

The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression.

Development of chromaffin cells depends on MASH1 function

Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4729-4738 ◽  
Author(s):  
Katrin Huber ◽  
Barbara Brühl ◽  
François Guillemot ◽  
Eric N. Olson ◽  
Uwe Ernsberger ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Adrenal Glands ◽  
Sympathetic Neurons ◽  
Cell Lineage ◽  
Neuroendocrine Differentiation ◽  
Sympathetic Ganglia ◽  
Adrenal Chromaffin Cells ◽  
Wild Type ◽  
Adrenal Chromaffin

The sympathoadrenal (SA) cell lineage is a derivative of the neural crest (NC), which gives rise to sympathetic neurons and neuroendocrine chromaffin cells. Signals that are important for specification of these two types of cells are largely unknown. MASH1 plays an important role for neuronal as well as catecholaminergic differentiation. Mash1 knockout mice display severe deficits in sympathetic ganglia, yet their adrenal medulla has been reported to be largely normal suggesting that MASH1 is essential for neuronal but not for neuroendocrine differentiation. We show now that MASH1 function is necessary for the development of the vast majority of chromaffin cells. Most adrenal medullary cells in Mash1–/– mice identified by Phox2b immunoreactivity, lack the catecholaminergic marker tyrosine hydroxylase. Mash1 mutant and wild-type mice have almost identical numbers of Phox2b-positive cells in their adrenal glands at embryonic day (E) 13.5; however, only one-third of the Phox2b-positive adrenal cell population seen in Mash1+/+ mice is maintained in Mash1–/– mice at birth. Similar to Phox2b, cells expressing Phox2a and Hand2 (dHand) clearly outnumber TH-positive cells. Most cells in the adrenal medulla of Mash1–/– mice do not contain chromaffin granules, display a very immature, neuroblast-like phenotype, and, unlike wild-type adrenal chromaffin cells, show prolonged expression of neurofilament and Ret comparable with that observed in wild-type sympathetic ganglia. However, few chromaffin cells in Mash1–/– mice become PNMT positive and downregulate neurofilament and Ret expression. Together, these findings suggest that the development of chomaffin cells does depend on MASH1 function not only for catecholaminergic differentiation but also for general chromaffin cell differentiation.

NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells

1990 ◽  
Vol 73 (3) ◽  
pp. 418-428 ◽  
Author(s):  
Jeffrey H. Kordower ◽  
Massimo S. Fiandaca ◽  
Mary F. D. Notter ◽  
John T. Hansen ◽  
Don M. Gash
Keyword(s):  
Tyrosine Hydroxylase ◽  
Adrenal Medulla ◽  
Sural Nerve ◽  
Chromogranin A ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Adrenal Chromaffin Cells ◽  
Content Type ◽  
Adrenal Chromaffin ◽  
Fine Print

✓ Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.

Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve

1996 ◽  
Vol 84 (4) ◽  
pp. 685-689 ◽  
Author(s):  
Isao Date ◽  
Takashi Imaoka ◽  
Yasuyuki Miyoshi ◽  
Takeshi Ono ◽  
Shoji Asari ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Nerve ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Caudate Nuclei ◽  
Modest Improvement ◽  
Content Type ◽  
Grafting Procedure

✓ A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase—immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.

Functional mitochondria are required for O2 but not CO2 sensing in immortalized adrenomedullary chromaffin cells

2008 ◽  
Vol 294 (4) ◽  
pp. C945-C956 ◽  
Author(s):  
J. Buttigieg ◽  
S. T. Brown ◽  
M. Lowe ◽  
M. Zhang ◽  
C. A. Nurse
Keyword(s):  
Complex I ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Carbonic Anhydrase Ii ◽  
Adrenal Chromaffin Cells ◽  
Wild Type ◽  
Mitochondrial Complex ◽  
Adrenal Chromaffin Cell ◽  
Adrenal Chromaffin ◽  
First Time

Catecholamine (CAT) release from adrenomedullary chromaffin cells (AMC) in response to stressors such as low O2 (hypoxia) and elevated CO2/H+ is critical during adaptation of the newborn to extrauterine life. Using a surrogate model based on a v -myc immortalized adrenal chromaffin cell line (i.e., MAH cells), combined with genetic perturbation of mitochondrial function, we tested the hypothesis that functional mitochondria are required for O2 sensing. Wild-type MAH cells responded to both hypoxia and increased CO2 (hypercapnia) with K+ current inhibition and membrane depolarization. Additionally, these stimuli caused a rise in cytosolic Ca2+ and CAT secretion, determined by fura-2 spectrofluorimetry and carbon fiber amperometry, respectively. In contrast, mitochondria-deficient (ρ0) MAH cells were hypoxia insensitive, although responses to hypercapnia and expression of several markers, including carbonic anhydrase II, remained intact. Rotenone (1 μM), a mitochondrial complex I blocker known to mimic and occlude the effects of hypoxia in primary AMC, was effective in wild-type but not ρ0 MAH cells. These data demonstrate that functional mitochondria are involved in hypoxia-sensing by adrenal chromaffin cells. We also show for the first time that, like their neonatal chromaffin cell counterparts, MAH cells are CO2 sensors; however, this property is independent of functional mitochondria.

Differences In Utero in Activities of Catecholamine Biosynthetic Enzymes in Adrenals of Spontaneously Hypertensive Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 227s-230s ◽  
Author(s):  
G. Teitelman ◽  
R. A. Ross ◽  
T. H. Joh ◽  
D. J. Reis
Keyword(s):  
Adrenal Medulla ◽  
Spontaneously Hypertensive Rats ◽  
Sympathetic Ganglia ◽  
Biosynthetic Enzymes ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Catecholamine Biosynthesis ◽  
Sd Rats ◽  
Wistar Kyoto

1. We sought to determine if catecholamine biosynthetic enzymes of spontaneously hypertensive rats (SHR) differed from those of normotensive Wistar—Kyoto (WKY) and Sprague—Dawley (SD) control rats before birth. 2. By immunocytochemical and biochemical methods we compared strains for the time of appearance and maturation of the enzymes tyrosine hydroylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in sympathetic ganglia and adrenals. 3. The time of appearance of enzymes was identical in all three strains: TH and DBH first appeared in sympathetic ganglia on embryonic day 11 (E11) and in adrenal medulla on E16. PNMT, restricted to adrenal medulla, appeared later on E18. 4. The activity of adrenal TH prenatally on E18 and E21 and at day of birth (P1) in SHR was approximately two fold that in WKY or SD rats. In contrast PNMT was lower in SHR but only on E18. 5. Thus, although the timing of the first expression of adrenergic phenotypes is similar in SHR and normotensive controls, the differences in TH activity in adrenals suggest an enhanced biosynthetic capacity for catecholamines in this strain before birth. 6. We conclude that SHR differ from normotensive rats from the first expression of some of the genes controlling catecholamine biosynthesis.

Electrophysiological and morphological features underlying neurotransmission efficacy at the splanchnic nerve-chromaffin cell synapse of bovine adrenal medulla

2010 ◽  
Vol 298 (2) ◽  
pp. C397-C405 ◽  
Author(s):  
Antonio M. G. de Diego
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Splanchnic Nerve ◽  
Staining Technique ◽  
Firing Frequency ◽  
Cholinergic Innervation ◽  
Bovine Adrenal Medulla ◽  
Acetylcholinesterase Staining ◽  
Few Data

The ability of adrenal chromaffin cells to fast-release catecholamines relies on their capacity to fire action potentials (APs). However, little attention has been paid to the requirements needed to evoke the controlled firing of APs. Few data are available in rodents and none on the bovine chromaffin cell, a model extensively used by researchers. The aim of this work was to clarify this issue. Short puffs of acetylcholine (ACh) were fast perifused to current-clamped chromaffin cells and produced the firing of single APs. Based on the currents generated by such ACh applications and previous literature, current waveforms that efficiently elicited APs at frequencies up to 20 Hz were generated. Complex waveforms were also generated by adding simple waveforms with different delays; these waveforms aimed at modeling the stimulation patterns that a chromaffin cell would conceivably undergo upon strong synaptic stimulation. Cholinergic innervation was assessed using the acetylcholinesterase staining technique on the supposition that the innervation pattern is a determinant of the kind of stimuli chromaffin cells can receive. It is concluded that 1) a reliable method to produce frequency-controlled APs by applying defined current injection waveforms is achieved; 2) the APs thus generated have essentially the same features as those spontaneously emitted by the cell and those elicited by fast-ACh perifusion; 3) the higher frequencies attainable peak at around 30 Hz; and 4) the bovine adrenal medulla shows abundant cholinergic innervation, and chromaffin cells show strong acetylcholinesterase staining, consistent with a tight cholinergic presynaptic control of firing frequency.

SYNTHESIS AND STORAGE OF PRESSOR AMINES IN ADRENAL MEDULLARY GRAFTS

1959 ◽  
Vol 18 (2) ◽  
pp. 162-NP ◽  
Author(s):  
R. E. COUPLAND
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Histochemical Methods ◽  
Significant Difference ◽  
Catechol Amines ◽  
And Storage

SUMMARY Auto- and homografts of adrenal medullae depleted of reserpine were used in order to follow the rate of synthesis and storage of pressor amines in non-innervated chromaffin cells. The changes were followed by histochemical methods. The findings indicate that there is no significant difference between the rate of storage of catechol amines in the implanted chromaffin cell and in the normal adrenal medulla.

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