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, Giuseppina; Rossi, Gian Paolo; Rebuffat, Piera; Malendowicz, Ludwik K.; Markowska, Anna; Nussdorfer, Gastone G.

doi:10.1210/endo.138.6.5191

Cited by 47 publications

(30 citation statements)

References 40 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis of all the components of the ET system in the zona glomerulosa, the proliferative layer involved in the growth of the entire adrenal cortex, suggests that the ET system is involved in this biological effect. This was recently demonstrated by Mazzochi et al (1997), who found that ETs stimulate the proliferation of rat adrenal zona glomerulosa cells via ET-A receptors. The use of a sensitive, specific RNA probe and a specific polyclonal antibody made it possible to map in detail the cellular distribution of ECE-1 mRNA and protein in the cells of a variety of human tissues.…”

Section: Discussionmentioning

confidence: 62%

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

Korth

Bohle

Corvol

et al. 1999

J Histochem Cytochem.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 62%

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

Korth

Bohle

Corvol

et al. 1999

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…14 ET-1 acts as secretagogue for calf adrenal zona glomerulosa cells 25 and is trophic for rat adrenal zona glomerulosa cells. 26 These authors suggested that ET-1 could be the factor that causes enhanced aldosterone secretion in APAs. The decrease in ET B receptors reported by Rossi et al 27 and Zeng et al 17 could cause the higher plasma ET-1 concentrations described by some, 16 as ET B may also function as a physiological clearance receptor for extracellular ET-1.…”

Section: Discussionmentioning

confidence: 99%

Localization of the Endothelin System in Aldosterone-Producing Adenomas

et al. 2001

View full text Add to dashboard Cite

Abstract-Endothelin-1 (ET-1) could play a role in the regulation of aldosterone secretion of the human adrenal gland. The presence of the endothelin-converting enzyme 1 (ECE-1) and ET-1 suggests that there is a local ET system in the adrenal cortex, but the in situ synthesis of ET-1 remains to be confirmed. The cellular distribution of the whole ET system was evaluated in 20 cases of aldosterone-producing adenomas. Polymerase chain reaction studies gave strong signals for ECE-1 mRNA and the mRNAs for endothelin type A (ET A ) and B (ET B ) receptors and faint signals for prepro-ET-1 mRNA. In situ hybridization showed ET A receptors scattered throughout the adenoma, in both secretory cells and vascular structures (score, ϩ). There were more ET B receptors (score, ϩϩ), but they were restricted mainly to the endothelium. ECE-1 mRNA and protein were ubiquitous and abundant in secretory cells (score, ϩϩϩ) and vascular structures (score, ϩϩ); the enzyme was active on big ET-1. There was no prepro-ET-1 mRNA in the cortex, except in the thickened precapillary arterioles present in only 30% of the aldosterone-producing adenomas studied. ET-1 immunoreactivity was detected in vascular structures (score, ϩ), probably bound to receptors, suggesting that ET-1 has an endocrine action. The low concentrations of ET-1 could also indicate that it acts in a paracrine-autocrine fashion to control adrenal blood flow. The discrepancy between the concentrations of ECE-1 and its substrate suggests that ECE-1 has another role in the adrenal secretory cells. Our data indicate that ET probably is not a primary cause of the development or maintenance of the adenoma. Key Words: endothelin Ⅲ hypertension, endocrine Ⅲ receptors, endothelin Ⅲ regional blood flow Ⅲ immunohistochemistry E ndothelin-1 (ET-1) is one of three 21-amino acid peptides, the ETs (ET-1, ET-2, and ET-3), that mediate a broad spectrum of biologic actions, such as the regulation of endocrine secretion. 1 It also is involved in specific vascular lesions and inflammatory conditions (primary and malignant hypertension). 2 The ETs act on 2 distinct high-affinity G protein-coupled receptors, endothelin type A (ET A ) 3 and type B (ET B ), 4 and are synthesized as large precursor polypeptides, the prepro-ETs, which are cleaved at 2 pairs of basic amino acids to generate intermediate peptides, the big ETs. The big ETs are then cleaved by an endothelin-converting enzyme (ECE), initially purified from bovine adrenal cortex, 5 to produce the mature ETs. Two human ECE genes have been cloned, ECE-1 6 and ECE-2, 7 and they are 59% identical.ET-1 was first found in the vascular endothelium, 8 but it is also present in endocrine tissues, such as the adrenal gland, 9 where it may mediate the adrenocortical response to ACTH. 10 Large amounts of ECE-1 mRNA and protein have been found in the human adrenal gland, with the highest concentrations in the zona glomerulosa and fasciculata. 11 Both ET receptor subtypes and ET peptides are found in the human adrenal gland. 9 The mRNAs for ET A , ET B ...

show abstract

“…ET family ligands, which include endothelin-1 (ET-1), vasoactive intestinal contractor (VIC)/endothelin-2 (ET-2), and endothelin-3 (ET-3), are peptides composed of 21 amino acid residues. These isopeptides have a variety of biological roles, including involvement in vasoconstriction (Yanagisawa et al 1988), bronchial smooth muscle contraction (Mckay et al 1991), and cell growth (Lahav et al 1996, Mazzocchi et al 1997. The effects of these peptides are mediated by receptors (ETRs) that are classified into two subtypes, the endothelin A receptor (ETA) and the endothelin B receptor (ETB).…”

Section: Introductionmentioning

confidence: 99%

Gene expression of vasoactive intestinal contractor/endothelin-2 in ovary, uterus and embryo: comprehensive gene expression profiles of the endothelin ligand-receptor system revealed by semi-quantitative reverse transcription-polymerase chain reaction analysis in adult mouse tissues and during late embryonic development

Uchide

Masuda²,

Mitsui³

et al. 1999

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Vasoactive intestinal contractor (VIC)/endothelin-2 (ET-2) is a 21 amino acid intestinal peptide characterized as a potent vasoactive and intestinal smooth muscle-contracting compound. To investigate the physiological roles of VIC/ET-2 further, we characterized the specificity of VIC gene expression relative to that of other members of the endothelin (ET) ligand-receptor system in adult mouse tissues and during embryonic development. Gene expression of ET-1, ET-3, ETA and ETB was ubiquitous in almost all tissues we examined while gene expression of VIC was localized to certain tissues. A high level of VIC gene expression was observed in ovary and uterus. The gene expression of VIC, relative to that of glyceraldehyde-3-phosphate dehydrogenase, was approximately 2·0%, 0·4%, and 2·3% in ovary, uterus, and intestine respectively, and was approximately 1·6 and 7·1 times higher than that of ET-1 in ovary and intestine respectively. Thus, VIC may have some physiological role in adult ovary and uterus as well as intestine. In embryonic development, VIC gene expression sharply increased between 11 and 15 days post coitus and decreased after birth, suggesting an involvement in the later stages of embryonic development.

show abstract

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

Cited by 47 publications

References 40 publications

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

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

Localization of the Endothelin System in Aldosterone-Producing Adenomas

Contact Info

Product

Resources

About