Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas

Abstract

Sst(5) and especially D(2) are highly expressed in the majority of human corticotroph adenomas, with coexpression of sst(5) and D(2) being a common phenomenon. These findings support the current studies with sst(5) and D(2)-targeting agents in patients with CD and highlight the rationale behind sst(5)-D(2) combination therapy.

New developments in the medical treatment of Cushing's syndrome

“…In recent years, dopamine receptors and somatostatin receptors have been identified as therapeutic targets on corticotroph adenomas (de Bruin et al 2009b). Approximately 80% of ACTH-secreting pituitary adenomas express the dopamine receptor subtype 2 (D 2 R; Pivonello et al 2004, de Bruin et al 2009b.…”

“…Approximately 80% of ACTH-secreting pituitary adenomas express the dopamine receptor subtype 2 (D 2 R; Pivonello et al 2004, de Bruin et al 2009b. Cabergoline is an ergot-derived dopamine agonist with particular high affinity for the D 2 R. Both in vitro and in vivo studies showed that cabergoline was efficacious with respect to inhibition of ACTH and cortisol secretion (discussed the 'Medical therapy for different causes of CS-Pituitary-dependent CS' section below).…”

“…To date, five somatostatin receptor subtypes (sst) have been identified (Patel 1999). Corticotroph pituitary adenomas predominantly express the sst 5 (de Bruin et al 2009b). In contrast to GH-producing pituitary adenomas, which have a high degree of sst 2 expression, sst 2 expression by corticotroph adenomas is low (de Bruin et al 2009b).…”

“…Corticotroph pituitary adenomas predominantly express the sst 5 (de Bruin et al 2009b). In contrast to GH-producing pituitary adenomas, which have a high degree of sst 2 expression, sst 2 expression by corticotroph adenomas is low (de Bruin et al 2009b). This explains why the sst 2 -targeting somatostatin analogs octreotide and lanreotide are generally ineffective in the treatment of CD (Lamberts et al 1989, Stalla et al 1994.…”

“…As already described in 'Pituitary-targeted drugs' section, ACTH-secreting pituitary adenomas predominantly express D 2 R and sst 5 , which can serve as targets for medical therapy (Pivonello et al 2004, de Bruin et al 2009b. Recently, three studies were published in which the effects of cabergoline monotherapy in patients with CD were evaluated (Pivonello et al 2009, Godbout et al 2010, Vilar et al 2010).…”