Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas.

Abstract

Thirty one pituitary adenomas and 3 samples of peritumoral anterior pituitary tissue were immunostained with an antibody raised against dopamine D2 receptor protein. The positive reactions were found in cell cytoplasm, a subpopulation of cell nuclei and the intratumoral blood vessels walls. As expected, the positive immunostaining was shown in cytoplasm and/or cell nuclei of all examined prolactinomas (7/7). In acromegaly the positive D2 staining occurred in 5/7 samples, in gonadotropinomas in 6/8 and in plurihormonal adenomas 2/4. The lowest expression was observed in corticotropinomas (1/5). These findings corroborate with the well known efficacy of D2 agonists in the treatment of prolactinomas and somatotropinomas, and support the rationale of the therapeutic trials with these compounds in gonadotropinomas. Moreover, the presence of D2 receptors in intratumoral blood vessels walls constitutes the possibility of the anti-angiogenic action of D2 agonists in pituitary adenomas.

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

“…The expression of D 2 R protein was found to be highly (36,37), but occasional immunostaining of the cell membrane has been observed (38). It remains to be determined whether cytoplasmic or membranebound D 2 R is closely correlated with responses to dopamine agonists and receptor internalisation.…”

Ocena efektów leczenia analogami somatostatyny nieczynnych hormonalnie gruczolaków przysadki w porównaniu z akromegalią

“…Because of strong immunostaining of SSTR1, which was present in 66% of examined cases of NFPA, we think that introduction of novel broad-spectrum somatostatin analogues would be more effective in the therapy of NFPA [20]. Moreover, considering tumour shrinkage, combined therapy with novel somatostatin analogues and dopamine agonists can presumably be more effective because NFPA are also characterised by the expression of dopamine receptor D2 [21,22].…”

Dopamine agonist-responsive Cushing’s disease

“…For most other pituitary tumours, surgery may be needed for various indications such as removal of the source of hormone secretion with the aim of achieving a cure, relief of compressive symptoms, especially optic nerve compression and recovery of the impaired pituitary function. Corticotropinomas have the lowest expression of D2 receptors making dopamine agonist the least effective option 2. However, medical treatment with a dopamine agonist can be successful in normalising ACTH excess in a rare case of ACTH and prolactin co-secretion as described herein.…”

“…Plurihormonal pituitary adenomas may be more common in patients with MEN1 (hereditary endocrine tumour syndrome with increased propensity to develop tumours in various organs, particularly in parathyroid, pituitary and/or pancreas), whereby a prolactin-producing adenoma with growth hormone (GH) co-secretion is the most common subtype among plurihormonal pituitary tumours. While the expression of GH and prolactin is regulated by the same transcription factors, a combination of prolactin and adrenocorticotropic hormone (ACTH) secretion is very rare as ACTH and prolactin expression is regulated by diverse pathways 2…”