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 (D(2)), 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 D(2) 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 D(2)
isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-
ligand binding study, using the radiolabeled D(2) analog (125)I-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 D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) 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. D(2), D(4), and D(5) were expressed in
pheochromocytomas. In all D(2)-positive tissues, both D(2)
isoforms were expressed, with the exception of one case of
aldosterone-secreting
adenoma and the
cortisol-secreting
carcinomas, in which only the D(2long)
isoform was expressed. D(2)-like receptor expression was confirmed at receptor-
ligand binding study. At immunohistochemistry, D(2) 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, D(2) 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 D(1)-like and D(2)-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.