chromaffin tissue [keywords]
- Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions. [Journal Article, Review]
- Front Endocrinol (Lausanne) 2016.:98.
In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions.
- Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands. [Journal Article]
- Anal Chem 2016 Aug 2; 88(15):7493-9.
A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 × 3.5 μm(2)) separated by 200 μm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues.
- Mediastinal paraganglioma fed by the left circumflex artery. [JOURNAL ARTICLE]
- Interact Cardiovasc Thorac Surg 2016 Jul 1.
A 60-year-old male patient who previously underwent carotid and jugular paraganglioma resections was referred because of a mediastinal recurrence at the root of the great vessels. Coronary angiography confirmed the circumflex artery of the left coronary artery as the feeding artery of the tumour. The patient underwent surgery due to the tumour's location and malignant potential. Upon mass resection, histopathological examination characterized the tumour as a secondary paraganglioma. Neuroendocrine tumours arising from chromaffin tissues at the extra-adrenal paraganglions of the autonomic nervous system are termed paragangliomas. Clinically, they are divided into functional and non-functional types, depending on their catecholamine secretion. The mediastinal location is exceptional and its treatment is challenging.
- Studying the peripheral sympathetic nervous system and neuroblastoma in zebrafish. [Journal Article]
- Methods Cell Biol 2016.:97-138.
The zebrafish serves as an excellent model to study vertebrate development and disease. Optically clear embryos, combined with tissue-specific fluorescent reporters, permit direct visualization and measurement of peripheral nervous system formation in real time. Additionally, the model is amenable to rapid cellular, molecular, and genetic approaches to determine how developmental mechanisms contribute to disease states, such as cancer. In this chapter, we describe the development of the peripheral sympathetic nervous system (PSNS) in general, and our current understanding of genetic pathways important in zebrafish PSNS development specifically. We also illustrate how zebrafish genetics is used to identify new mechanisms controlling PSNS development and methods for interrogating the potential role of PSNS developmental pathways in neuroblastoma pathogenesis in vivo using the zebrafish MYCN-driven neuroblastoma model.
- [Pheochromocytoma and pregnancy. A case report]. [English Abstract, Journal Article]
- Ginecol Obstet Mex 2015 Nov; 83(11):735-42.
Pheochromocytoma is a tumor originating in the chromaffin cells. These tumors secrete catecholamines which act on target organs and cause hypertensive crises. They are rare during pregnancy, and a differential diagnosis must be carried out mainly with pregnancy-induced hypertension.A 22-year-old patient in week 11.5 of pregnancy presented at the Hospital General Dr. Miguel Silva in Morelia, Michoacán with hypertension that had existed for more than two years with poor adherence to treatment. At the time of referral to our unit she presented a hypertensive crisis that had been unresponsive to all antihypertensive treatments. Following the establishment of a study protocol, a diagnosis of posterior left adrenal pheochromocytoma was made. After subsequent pharmacological treatment with alpha and beta blockers, a left adrenalectomy was performed. The patient did not require antihypertensive treatment following surgery. The histopathological report indicates the presence of a nodular and vascularized left adrenal gland weighing 25 g and measuring 5 x 4 x 3.5 cm. Gland consistency was soft, and the presence of cystic lesions in parenchymal tissue was noted. A yellowish-brown color and sponge-like appearance were also present. Such features support a diagnosis of pheochromocytoma. The pregnancy continued normally until week 32, when the patient presented to our department with active-phase preterm labor. A Cesarean section was performed with the delivery of a live female weighing 1400 gr. The infant is currently alive and well.Thus, it is important that obstetrician knows this disease and its management during pregnancy; so we present this case report.
- Morphology, Biochemistry, and Pathophysiology of MENX-Related Pheochromocytoma Recapitulate the Clinical Features. [Journal Article]
- Endocrinology 2016 Aug; 157(8):3157-66.
Pheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Because such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, we characterized a spontaneous animal model (multiple endocrine neoplasia [MENX] rats) that develops endogenous PCCs with complete penetrance. Urine was longitudinally collected from wild-type (wt) and MENX-affected (mutant) rats and outputs of catecholamines and their O-methylated metabolites determined by mass spectrometry. Adrenal catecholamine contents, cellular ultrastructure, and expression of phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine, were also determined in wt and mutant rats. Blood pressure was longitudinally measured and end-organ pathology assessed. Compared with wt rats, mutant animals showed age-dependent increases in urinary outputs of norepinephrine (P = .0079) and normetanephrine (P = .0014) that correlated in time with development of tumor nodules, increases in blood pressure, and development of hypertension-related end-organ pathology. Development of tumor nodules, which lacked expression of N-methyltransferase, occurred on a background of adrenal medullary morphological and biochemical changes occurring as early as 1 month of age and involving increased adrenal medullary concentrations of dense cored vesicles, tissue contents of both norepinephrine and epinephrine, and urinary outputs of metanephrine, the metabolite of epinephrine. Taken together, MENX-affected rats share several biochemical and pathophysiological features with PCC patients. This model thus provides a suitable platform to study the pathogenesis of PCC for preclinical translational studies aimed at the development of novel therapies for aggressive forms of human tumors.
- Laparoscopic resection of a large paraganglioma arising in the organ of Zuckerkandl: Report of a case and review of the literature. [JOURNAL ARTICLE]
- J Minim Access Surg 2016 Jun 2.
Paragangliomas are catecholamine-secreting neuroendocrine tumours arising from chromaffin tissue at extra-adrenal sites. The commonest site for a paraganglioma is the organ of Zuckerkandl. Traditional treatment of paraganglioma of organ of Zuckerkandl (POZ) involves open surgical resection, and only a few cases of laparoscopic approach to this pathology have been reported. We report the successful laparoscopic resection of a large POZ in a 22-year-old woman and review the previous cases reporting a laparoscopic approach to this rare tumour.
- MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells. [Journal Article]
- Cell Tissue Res 2016 Aug; 365(2):225-32.
The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR-124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non-neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells.
- Primary hypercortisolism and phaeochromocytoma next to, but not related to, each other. [Journal Article]
- BMJ Case Rep 2016.:10.1136/bcr-2015-213359.
This is the first report of unilateral hypercortisolism and phaeochromocytoma that cannot be explained by medullary tumourigenic adrenocorticotropic hormone (ACTH) excretion. The patient was referred for an adrenal incidentaloma with hypertension but no Cushingoid features, disturbed glucose tolerance and osteopaenia. Additional testing revealed hypercortisolism with suppressed ACTH, and a right-sided phaeochromocytoma with typical radiographic appearance. Resection of the right adrenal completely normalised the clinical symptoms and biochemistry, and increased ACTH concentrations, implicating initial suppression. Histology revealed a tumour consisting of chromaffin cells, with only pre-existing cortical tissue containing groups of ACTH-positive cells. Recent human studies in primary Cushing's syndrome demonstrated that a paracrine effect of these aberrant cells, assumed to be Leydig cells in origin, results in hypercortisolism by stimulation of surrounding steroidogenic cells, leading to systemic ACTH suppression. We propose that 2 diagnoses within 1 adrenal, being phaeochromocytoma and autonomous cortisol overproduction due to adjoining aberrant ACTH-producing cells, explain the clinical picture.
- Non-Functional Paraganglioma of the Urinary Bladder Treated by Transurethral Resection: Report of Two Cases. [Journal Article]
- J Clin Diagn Res 2016 Feb; 10(2):XD01-XD03.
Paraganglioma of the urinary bladder is a rare tumour derived from chromaffin tissue of the sympathetic nervous system. Paraganglioma of the urinary bladder especially the non-functional type is often misdiagnosed as urothelial cancer. Two female patients aged 32 years and 45 years presented with painless haematuria without any symptoms of catecholamine excess. Radiological investigations revealed urinary bladder tumour. The tumour was removed by transurethral resection in both the patients. Histopathological diagnosis was paraganglioma, which was confirmed by immunohistochemistry. Complete resection of tumour by transurethral approach is curative in paraganglioma of the urinary bladder. We hereby, also discuss the salient features of nonfunctional paraganglioma of the urinary bladder.