ABSTRACT
OBJECTIVES: The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists. DESIGN: Together with an extensive description of the clinical history of this case, a combination of in vitro and in vivo techniques was performed to provide the basis of the dopamine resistance developed in the course of the disease. METHOD: A comparison of the D2R was performed in specimens obtained at presentation of the disease compared with autoptic specimens derived from local invasion and metastasis using in situ hybridization and immunohistochemical techniques. RESULTS: Intact D2R mRNA was found in the primitive tumor and metastatic tissues, whereas protein for the same receptor was present only in the tissues derived from neurosurgical operations and not in the metastases obtained post-mortem. CONCLUSION: This is the first report of the absence of D2R protein despite the retention of the transcript in an advanced stage of a malignant prolactinoma. The findings of this single case suggest the hypothesis that postranscriptional mechanisms may contribute to the development of dopamine resistance in prolactinomas.
Subject(s)
Brain Neoplasms/secondary , Neoplasm Proteins/metabolism , Pituitary Neoplasms/metabolism , Prolactinoma/metabolism , RNA, Messenger/biosynthesis , Receptors, Dopamine D2/biosynthesis , Spinal Neoplasms/secondary , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Bromocriptine/therapeutic use , Dopamine Agonists/therapeutic use , Humans , Immunohistochemistry , In Situ Hybridization , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Proteins/cerebrospinal fluid , Pituitary Neoplasms/cerebrospinal fluid , Pituitary Neoplasms/pathology , Prolactin/blood , Prolactinoma/cerebrospinal fluid , Prolactinoma/pathology , RNA, Messenger/cerebrospinal fluid , Spinal Neoplasms/metabolism , Spinal Neoplasms/pathology , Vision Disorders/etiologyABSTRACT
The cerebrospinal fluid (CSF) of patients with hypophysis adenomas was used to investigate its effect on organotypic cultures of dorsal root ganglia (DRG) of 10-11 day old chick embryo. Only the CSF from patients with prolactinoma showed a neurite-stimulating effect compared with other hypophysis adenomas.
Subject(s)
Ganglia, Spinal/physiology , Neurites/physiology , Neurons, Afferent/ultrastructure , Pituitary Neoplasms/cerebrospinal fluid , Prolactinoma/cerebrospinal fluid , Animals , Cerebrospinal Fluid/physiology , Chick Embryo , Humans , Organ Culture TechniquesABSTRACT
Prolactine was found to promote neurite extension in chick embryo dorsal root ganglia in vitro. This hormone was active at the concentration 10-50 ng/ml provided extensive neurite outgrowth in the bioassay, compared to the control. The liquor from patients with prolactinoma was also found to promote neurite extension. This fact may be used for prolactinoma diagnostics.
