Affiliation:
1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
2. The Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235
Abstract
Abstract
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 ETB 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.
Reference38 articles.
1. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin.;Moncada;Pharmacol Rev,1979
2. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.;Furchgott;Nature,1980
3. Vascular endothelial cells synthesize nitric oxide from l-arginine.;Palmer;Nature,1988
4. Release of NO and EDRF from cultured bovine aortic endothelial cells;Myers;Am J Physiol,1989
5. A novel potent vasoconstrictor peptide produced by vascular endothelial cells.;Yanagisawa;Nature,1988
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