&lt;b&gt;&lt;i&gt;IN VITRO&lt;/i&gt; AUTORADIOGRAPHIC DEMONSTRATION OF ENDOTHELIN-1 BINDING SITES IN THE HUMAN ADRENAL &lt;/b&gt;&lt;b&gt;CORTEX &lt;/b&gt;

Belloni, Anna S.; Rossi, Gian Paolo; Zanin, Lucia; Prayer-Galetti, Tommaso; Pessina, Achille C.; Nussdorfer, Gastone G.

doi:10.2220/biomedres.15.95

Cited by 14 publications

(3 citation statements)

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“…There was an ECE-1 gradient accross the zones of the adrenal gland, with the zona glomerulosa having the highest staining. Autoradiography has shown that ET-A receptors are limited exclusively to the zona glomerulosa, whereas ET-B receptors are found throughout the adrenal cortex (Belloni et al 1994). Davenport et al (1996) found that ET peptides and receptors were differentially distributed in the human adrenal gland.…”

Section: Discussionmentioning

confidence: 99%

Cellular Distribution of Endothelin-converting Enzyme-1 in Human Tissues

Korth

Bohle

Corvol

et al. 1999

J Histochem Cytochem.

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SUMMARY Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin biosynthesis, catalyzing the final processing step. As shown by the targeted disruption of the ECE-1 gene, mature endothelins must be produced at specific sites for normal embryonic development. Therefore, it is important to know the exact pattern of ECE-1 gene expression. In this study we investigated the cellular distribution of ECE-1 in a variety of human tissues by in situ hybridization and immunohistochemistry. Widespread expression of the ECE-1 gene was noted, with a similar distribution pattern for mRNA and protein in normal human tissues, suggesting a major biological role for ECE-1. ECE-1 levels were particularly high in the cardiovascular, reproductive, and endocrine systems. There was strong and consistent labeling for ECE-1 in the vascular endothelial cells of all organs examined and in various nonvascular cells, especially some glandular cells. A large amount of ECE-1 protein and mRNA was detected in the Leydig cells of the testis and in the granulosa and theca cells of the ovary. In the adrenal gland, ECE-1 was detected in the cortex and medulla, with the strongest labeling in the zona glomerulosa. Therefore, ECE-1 may be involved in other systems, such as the regulation of hormone secretion, rather than exclusively generating ET-1 from its precursor. These results point out the potential side effects of ECE-1 inhibitors that are currently under development for treatment of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Cellular Distribution of Endothelin-converting Enzyme-1 in Human Tissues

Korth

Bohle

Corvol

et al. 1999

J Histochem Cytochem.

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“…Clearly, the two endocrine systems within the adrenal form a functional unit, and an alteration in one system will certainly affect the other (15). It has recently been demonstrated that chromaffin cells are in close cellular contact with adrenocortical cells (14, 36 -38), immune cells (39,40), nerve cells (41), and endothelial cells (42) in normal adrenals. These paracrine intra-adrenal interactions within dif-ferent components of the adrenal are important for basal hormone production and play a role in the development, cell proliferation, circadian rhythm and zonation of the adrenal gland (15,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullary function is severely impaired in 21‐hydroxylase‐deficient mice

et al. 1999

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Deficiency of 21-hydroxylase (21-OH), one of the most common genetic defects in humans, causes low glucocorticoid and mineralocorticoid production by the adrenal cortex, but the effect of this disorder on the adrenomedullary system is unknown. Therefore, we analyzed the development, structure, and function of the adrenal medulla in 21-OH-deficient mice, an animal model resembling human congenital adrenal hyperplasia. Chromaffin cells of 21-OH-deficient mice exhibited ultrastructural features of neuronal transdifferentiation with reduced granules, increased rough endoplasmic reticulum and small neurite outgrowth. Migration of chromaffin cells in the adrenal to form a central medulla was impaired. Expression of phenylethanolamine-N-methyltransferase (PNMT) was reduced to 27 +/- 9% (P<0.05), as determined by quantitative TaqMan polymerase chain reaction, and there was a significant reduction of cells staining positive for PNMT in the adrenal medulla of the 21-OH-deficient mice. Adrenal contents of epinephrine were decreased to 30 +/- 2% (P<0. 01) whereas norepinephrine and dopamine levels were reduced to 57 +/- 4% (P<0.01) and 50 +/- 9% (P<0.05), respectively. 21-OH-deficient mice demonstrate severe adrenomedullary dysfunction, with alterations in chromaffin cell migration, development, structure, and catecholamine synthesis. This hitherto unrecognized mechanism may contribute to the frequent clinical, mental, and therapeutic problems encountered in humans with this genetic disease.

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“…5). Accordingly, the autoradiographic quantitative analysis of [ 125 I]ET-1 binding and its displacement by selective ligands clearly demonstrated that ETB receptors are present throughout the entire adrenal cortex, whereas ETA receptors are restricted to the ZG (3,4,6,7).…”

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confidence: 99%

Endothelins Stimulate Deoxyribonucleic Acid Synthesis and Cell Proliferation in Rat Adrenal Zona Glomerulosa, Acting through an Endothelin A Receptor Coupled with Protein Kinase C- and Tyrosine Kinase-Dependent Signaling Pathways

Mazzocchi

Rossi²,

Rebuffat³

et al. 1997

Endocrinology

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The effects of endothelins (ET) on the proliferative activity of the rat adrenal cortex have been investigated in vivo, using an in situ perfusion technique of the intact left gland. The chemicals were dissolved in the perfusion medium, and the perfusion continued for 120 min. ET-1 concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; 6- and 3-fold increases, respectively, at a 10(-8) M concentration), but not in the inner adrenocortical layers, where the basal proliferative activity was negligible. The effect of 10(-8) M ET-1 was blocked by the ETA receptor antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET-2 and ET-3 (10(-8) M) enhanced DNA synthesis in the ZG, but their effects were less intense than that of 10(-8) M ET-1 and were directly related to their binding potency for the ETA receptor subtype (ET-1 > ET-2 >> ET-3). The selective ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were ineffective. The ZG proliferogenic action of 10(-8) M ET-1 was reversed by both the protein kinase C inhibitor Ro31-8220 and the tyrosine kinase inhibitor tyrphostin-23; a complete blockade was obtained at a 10(-6)-M concentration of each inhibitor. In contrast, neither the protein kinase A inhibitor H-89 (10(-5) M) nor the cyclooxygenase and lipoxygenase inhibitors indomethacin and phenidone (10(-5) M) affected ET-1 action. Collectively, our findings indicate that ETs stimulate the proliferation of rat adrenal ZG cells, acting through ETA receptors coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways. The results of the present study are in keeping with the view that in mammals, ZG is the proliferative layer involved in the maintenance of growth of the entire adrenal cortex and with the previous autoradiographic demonstration that ZG is the only adrenocortical layer provided with ETA receptors.

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<b><i>IN VITRO</i> AUTORADIOGRAPHIC DEMONSTRATION OF ENDOTHELIN-1 BINDING SITES IN THE HUMAN ADRENAL </b><b>CORTEX </b>

Cited by 14 publications

References 0 publications

Cellular Distribution of Endothelin-converting Enzyme-1 in Human Tissues

Cellular Distribution of Endothelin-converting Enzyme-1 in Human Tissues

Adrenomedullary function is severely impaired in 21‐hydroxylase‐deficient mice

Endothelins Stimulate Deoxyribonucleic Acid Synthesis and Cell Proliferation in Rat Adrenal Zona Glomerulosa, Acting through an Endothelin A Receptor Coupled with Protein Kinase C- and Tyrosine Kinase-Dependent Signaling Pathways

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