Dopamine Receptor Expression and Function in Human Normal Adrenal Gland and Adrenal Tumors

Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D2), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The...

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Published in:The journal of clinical endocrinology and metabolism 2004-09, Vol.89 (9), p.4493-4502
Main Authors: Pivonello, Rosario, Ferone, Diego, de Herder, Wouter W, de Krijger, Ronald R, Waaijers, Marlijn, Mooij, Diana M, van Koetsveld, Peter M, Barreca, Antonina, Del Basso De Caro, Maria Laura, Lombardi, Gaetano, Colao, Annamaria, Lamberts, Steven W. J, Hofland, Leo J
Format: Article
Language:English
Subjects:
Adrenal Gland Neoplasms - chemistry
Adrenal Glands - chemistry
Adrenocorticotropic Hormone - pharmacology
Adult
Aged
Aldosterone - secretion
Biological and medical sciences
Bromocriptine - pharmacology
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Humans
Immunohistochemistry
Male
Medical sciences
Middle Aged
Receptors, Dopamine - analysis
Receptors, Dopamine - physiology
Reverse Transcriptase Polymerase Chain Reaction
Vertebrates: endocrinology
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Summary:Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D2), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D2 localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D2 isoform (D2long and D2short) expression was evaluated by RT-PCR. D2 localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D2-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D2 analog 125I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D1-like and D2-like receptors were expressed in all normal and hyperplastic adrenals. D2 and D4 were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D2, D4, and D5 were expressed in pheochromocytomas. In all D2-positive tissues, both D2 isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisolsecreting carcinomas, in which only the D2long isoform was expressed. D2-like receptor expression was confirmed at receptor-ligand binding study. At immunohistochemistry, D2 was mainly localized in the zona glomerulosa and reticularis of the adrenal cortex and, to a lesser extent, in the zona fasciculata and medulla of normal and hyperplastic adrenal tissue. In the positive tumors, D2 was localized in the tu
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2003-031746