Adrenal capillary endothelial cells stimulate aldosterone release through a protein that is distinct from endothelin. Endocrinology 1999 Oct;140(10):4411-8
Date
09/28/1999Pubmed ID
10499493DOI
10.1210/endo.140.10.7060Scopus ID
2-s2.0-0033305742 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
We tested the possibility that bovine adrenal capillary endothelial cells (ECs) stimulate aldosterone secretion from bovine zona glomerulosa (ZG) cells by the release of a transferable factor. In coincubations of ZG cells and ECs in serum-free medium, aldosterone release was stimulated approximately 17-fold, and the stimulation was related to the concentration of ECs. The maximal stimulation by ECs was 75% of the maximal response to ACTH. In contrast, adrenal pericytes and fibroblasts were without effect. ECs incubated alone without ZG cells did not produce aldosterone. Conditioned medium from ECs (EC-CM), but not adrenal fibroblasts, stimulated aldosterone release approximately 3-fold. The stimulation increased with the concentration of EC-CM and the duration of conditioning time. Steroidogenic activity in EC-CM was abolished by pronase treatment, indicating that the active factor was a protein. However, the activity in EC-CM was distinct from that of endothelin-1 (ET-1), an endothelial peptide that also stimulates aldosterone secretion, as it was not blocked by the ET(B) receptor antagonist PD-145065, it did not alter [125I]ET-1 binding to ZG cells, and its release occurred before the release of ET-1. Neither ECs nor EC-CM stimulated the production of cortisol from zona fasciculata cells. The activity of EC-CM was not blocked by an angiotensin II AT1 receptor antagonist or a bradykinin B2 receptor antagonist. EC-CM stimulated increased intracellular calcium in fura-2-loaded ZG cells, but did not increase the production of cAMP. Using gel filtration, this peptide had an approximate molecular mass of 3000 Da and migrated earlier than ET-1. This study demonstrates that ECs in vitro alter steroidogenesis through the release of a transferable substance and suggests the existence of an endothelium-derived steroidogenic factor that is produced by adrenal capillary ECs. This endothelium-derived steroidogenic factor may function in the adrenal gland as a paracrine regulator of aldosterone secretion.
Author List
Rosolowsky LJ, Hanke CJ, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCraig J. Hanke PhD Assistant Dean, Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adrenal GlandsAdrenocorticotropic Hormone
Aldosterone
Angiotensin II
Animals
Bradykinin
Capillaries
Cattle
Coculture Techniques
Endothelin Receptor Antagonists
Endothelin-1
Endothelium, Vascular
Hormone Antagonists
Oligopeptides
Osmolar Concentration
Pronase
Receptor, Endothelin B
Steroids
Time Factors
Zona Fasciculata
Zona Glomerulosa