This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosolowsky, L. J. Articles by Campbell, W. B. Search for Related Content PubMed PubMed Citation Articles by Rosolowsky, L. J. Articles by Campbell, W. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Adrenal Capillary Endothelial Cells Stimulate Aldosterone Release through a Protein That Is Distinct from Endothelin¹

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; and the Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235

Address all correspondence and requests for reprints to: Dr. William B. Campbell, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226. E-mail: wbcamp{at}mcw.edu

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.

This article has been cited by other articles:

				D. X. Zhang, K. M. Gauthier, J. R. Falck, A. Siddam, and W. B. Campbell Steroid-Producing Cells Regulate Arterial Tone of Adrenal Cortical Arteries Endocrinology, August 1, 2007; 148(8): 3569 - 3576. [Abstract] [Full Text] [PDF]

				C. J. Hanke, B. B. Holmes, Y. Xu, K. Nithipatikom, and W. B. Campbell Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells Endocrinology, January 1, 2007; 148(1): 317 - 323. [Abstract] [Full Text] [PDF]

				K. Nithipatikom, B. B. Holmes, M. J. McCoy, C. J. Hillard, and W. B. Campbell Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E820 - E827. [Abstract] [Full Text] [PDF]

				D. X. Zhang, K. M. Gauthier, and W. B. Campbell Acetylcholine-Induced Relaxation and Hyperpolarization in Small Bovine Adrenal Cortical Arteries: Role of Cytochrome P450 Metabolites Endocrinology, October 1, 2004; 145(10): 4532 - 4539. [Abstract] [Full Text] [PDF]

				D. X. Zhang, K. M. Gauthier, and W. B. Campbell Characterization of Vasoconstrictor Responses in Small Bovine Adrenal Cortical Arteries in Vitro Endocrinology, April 1, 2004; 145(4): 1571 - 1578. [Abstract] [Full Text] [PDF]

				C. J. Hanke and W. B. Campbell Endothelial cell nitric oxide inhibits aldosterone synthesis in zona glomerulosa cells: modulation by oxygen Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E846 - E854. [Abstract] [Full Text] [PDF]