Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors

Rosario Pivonello, Diego Ferone, Wouter W. De Herder, Ronald R. De Krijger, Marlijn Waaijers, Diana M. Mooij, Peter M. Van Koetsveld, Antonina Barreca, Maria Laura Del Basso De Caro, Gaetano Lombardi, Annamaria Colao, Steven W J Lamberts, Leo J. Hofland

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Abstract

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 non-tumoral 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 D 2 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 D 2-positive tissues, both D2 isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisol-secreting 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 tumoral cells. At the in vitro study, a significant inhibition of both baseline and ACTH-stimulated aldosterone secretion was found after high-dose cabergoline, but not bromocriptine, administration; and a significant inhibition of angiotensin-II-stimulated aldosterone secretion was found after both bromocriptine and cabergoline administration in the adrenal hyperplasias. In conclusion, the current study demonstrated that both D1-like and D2-like receptors are expressed in the normal adrenal gland and in a percentage of adrenal adenomas or carcinomas. Bromocriptine and cabergoline induce only a minor inhibition of the secretion of adrenal hormones in the nontumoral adrenal gland in vitro, not excluding, however, the possible effective use of dopamine agonists in vivo in the treatment of adrenal tumors.

Original languageEnglish
Pages (from-to)4493-4502
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number9
DOIs
Publication statusPublished - Sep 2004

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Glandular and Epithelial Neoplasms
Dopamine Receptors
Adrenal Glands
Aldosterone
Tumors
Bromocriptine
Hydrocortisone
Adenoma
Carcinoma
Tissue
Hyperplasia
Protein Isoforms
Dopamine Agonists
Pheochromocytoma
Angiotensin II
Adrenocorticotropic Hormone
Androgens
Immunohistochemistry
Zona Reticularis
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Pivonello, R., Ferone, D., De Herder, W. W., De Krijger, R. R., Waaijers, M., Mooij, D. M., ... Hofland, L. J. (2004). Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors. Journal of Clinical Endocrinology and Metabolism, 89(9), 4493-4502. https://doi.org/10.1210/jc.2003-031746

Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors. / 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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 9, 09.2004, p. 4493-4502.

Research output: Contribution to journalArticle

Pivonello, R, Ferone, D, De Herder, WW, De Krijger, RR, Waaijers, M, Mooij, DM, Van Koetsveld, PM, Barreca, A, Del Basso De Caro, ML, Lombardi, G, Colao, A, Lamberts, SWJ & Hofland, LJ 2004, 'Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors', Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 9, pp. 4493-4502. https://doi.org/10.1210/jc.2003-031746
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. / Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89, No. 9. pp. 4493-4502.
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T1 - Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors

AU - Pivonello, Rosario

AU - Ferone, Diego

AU - De Herder, Wouter W.

AU - De Krijger, Ronald R.

AU - Waaijers, Marlijn

AU - Mooij, Diana M.

AU - Van Koetsveld, Peter M.

AU - Barreca, Antonina

AU - Del Basso De Caro, Maria Laura

AU - Lombardi, Gaetano

AU - Colao, Annamaria

AU - Lamberts, Steven W J

AU - Hofland, Leo J.

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N2 - 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 non-tumoral 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 D 2 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 D 2-positive tissues, both D2 isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisol-secreting 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 tumoral cells. At the in vitro study, a significant inhibition of both baseline and ACTH-stimulated aldosterone secretion was found after high-dose cabergoline, but not bromocriptine, administration; and a significant inhibition of angiotensin-II-stimulated aldosterone secretion was found after both bromocriptine and cabergoline administration in the adrenal hyperplasias. In conclusion, the current study demonstrated that both D1-like and D2-like receptors are expressed in the normal adrenal gland and in a percentage of adrenal adenomas or carcinomas. Bromocriptine and cabergoline induce only a minor inhibition of the secretion of adrenal hormones in the nontumoral adrenal gland in vitro, not excluding, however, the possible effective use of dopamine agonists in vivo in the treatment of adrenal tumors.

AB - 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 non-tumoral 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 D 2 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 D 2-positive tissues, both D2 isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisol-secreting 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 tumoral cells. At the in vitro study, a significant inhibition of both baseline and ACTH-stimulated aldosterone secretion was found after high-dose cabergoline, but not bromocriptine, administration; and a significant inhibition of angiotensin-II-stimulated aldosterone secretion was found after both bromocriptine and cabergoline administration in the adrenal hyperplasias. In conclusion, the current study demonstrated that both D1-like and D2-like receptors are expressed in the normal adrenal gland and in a percentage of adrenal adenomas or carcinomas. Bromocriptine and cabergoline induce only a minor inhibition of the secretion of adrenal hormones in the nontumoral adrenal gland in vitro, not excluding, however, the possible effective use of dopamine agonists in vivo in the treatment of adrenal tumors.

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