Preclinical and clinical experiences with the role of dopamine receptors in the treatment of pituitary adenomas

Abstract

Pituitary tumors can cause symptoms of mass effect and hormonal hypersecretion that can be reversed with surgical resection or debulking of the adenoma, radiotherapy, or medical treatment. Medical treatment is the primary choice for prolactinomas because dopamine agonists are very effective in the treatment of these tumors, with rates of control (tumor size reduction and hormone suppression) as high as 80-90% for microprolactinomas and 60-75% for macroprolactinomas. The function of dopamine receptors in other histotypes of pituitary adenoma is still debated. However, new insights into receptor physiology and the introduction of new clinically available, as well as experimental, compounds have reopened a potential role of dopaminergic drugs in the medical treatment of pituitary tumors. The differences between the effectiveness and the resistance to different dopaminergic agents, the new challenging results from clinical and experimental studies, as well as the future of dopamine agonists in the therapy of pituitary tumors are discussed. European Journal of Endocrinology 156 S37-S43

The role of somatostatin and dopamine D2 receptors in endocrine tumors

“…Recently, bromocriptine and cabergoline have been shown to be effective in suppressing ACTH secretion in a small group of patients with lung carcinoid (Reith et al 1987, Pivonello et al 2007a, as previously observed in vitro by Farrell et al (1992). Moreover, preliminary data by Pivonello et al (2008) demonstrated an in vitro inhibitory effect of cabergoline on cell growth in ten different cases of pancreatic endocrine tumors (seven cases defined as well-differentiated tumors and three defined as well-differentiated carcinomas).…”

“…Beyond the above-mentioned NET, the presence of DR -mainly D 2 -has been demonstrated in a small group of well-differentiated endocrine tumors (including lung and thymic carcinoids), associated with ectopic ACTH secretion and Cushing's syndrome (Pivonello et al 2007a).…”

“…Targeting D 2 has been shown as an effective mechanism for suppressing secretion of hormones by NET, and especially in pituitary adenomas (Ren et al 2003a, Pivonello et al 2004b, Jaquet et al 2005a, Ferone et al 2007a). In particular, in patients with prolactin-secreting pituitary adenomas, the role of D 2 agonist treatment is well established (i.e.…”

“…Behavioral and clinical evidence in brain research indicated an interaction between the somatostatinergic and dopaminergic systems (Chneiweiss et al 1985, Martin-Iverson et al 1986, Izquierdo-Claros et al 1997, Marzullo et al 1999, recently confirmed by in vitro studies (Rocheville et al 2000a, Baragli et al 2007, Kidd et al 2008. It is well known that SSTR and DR are widely expressed both in normal human neuroendocrine tissues and in tumors (Reubi et al 1987, Pivonello et al 2007b, such as pituitary adenomas (Stefaneanu et al 2001, Moller et al 2003, Saveanu et al 2008, Ferone et al 2009) and adrenal tumors (Pivonello et al 2007a,b, de Bruin et al 2009a. Since SSTR and D 2 -like receptors mainly exert inhibitory functions, medical therapies targeting these receptors with selective agonists have been developed for the treatment of a number of neuroendocrine disorders.…”

Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas.

“…Recently, the chimeric molecules acting simultaneously on somatostatin 2A and dopamine D2 receptors were developed and their enhanced potency in inhibiting both growth hormone and prolactin secretion was shown [9]. These compounds were also found to suppress in vitro the viability of cells isolated from the clinically nonfunctioning pituitary adenomas and were suggested as potential future medical treatment for this type of malignancies [8,10].…”