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Effect of Dopamine Agonists on Lactotroph Adenomas of the Human Pituitary
Lucia Stefaneanu1, Kalman Kovacs, Bernd W. Scheithauer
1MD, PHD.
Abstract:
Dopamine (DA) agonists cause reduction of blood prolactin level and tumor shrinkage in most patients with lactotroph adenoma. Our aim was to investigate the cellular mechanism of tumor shrinkage by determining mitotic, MIB-1, p27, and apoptotic indices, as well as microvessel density (MVD), surface microvessel density (SMD). ploidy, and other nuclear parameters. Surgically removed lactotroph adenomas were selected from 29 patients, of whom 19 were treated with oral bromocriptine (BEC), long-acting injectable BEC (BEC-LAR), or quinagolide and 10 were untreated. In treated adenomas mitotic and MIB-1 indices were lower, whereas the apoptotic indices were not significantly higher compared to untreated adenomas. The decrease in MIB-1 labeling reached significance in adenomas exposed to quinagolide (p<0.05). Aside from the BEC-LAR treated group, wherein p27 expression was significantly reduced (p<0.05), p27 expression did not differ significantly between the treated and untreated groups. MVD density was significantly lower in the treated adenomas, whereas the decrease in SMD did not attain significance. The DNA ploidy and most other nuclear parameters did not differ significantly in the two groups. In conclusion, reduction of mitotic and MIB-1 indices indicates that suppression of cell proliferation contributes to tumor shrinkage, whereas p27 protein expression and apoptosis play no major role in the adenoma involution. Further studies are required to explain the effect of DA agonists on MVD and SMD.
Insights
Dopamine agonists shrink lactotroph adenomas by reducing cell proliferation, indicated by lower mitotic and MIB-1 indices. Apoptosis and p27 expression do not significantly contribute to this tumor shrinkage.
Area of Science:
- Endocrinology
- Oncology
- Cell Biology
Background:
- Lactotroph adenomas are pituitary tumors often treated with dopamine agonists.
- Dopamine agonists effectively reduce prolactin levels and induce tumor shrinkage.
- The precise cellular mechanisms underlying dopamine agonist-induced tumor shrinkage require further elucidation.
Purpose of the Study:
- To investigate the cellular mechanisms responsible for tumor shrinkage in lactotroph adenomas treated with dopamine agonists.
- To compare cellular parameters including proliferation, apoptosis, and microvessel density between treated and untreated adenomas.
Main Methods:
- Analysis of surgically removed lactotroph adenomas from 29 patients (19 treated, 10 untreated).
- Assessment of mitotic index, MIB-1 labeling index, p27 expression, apoptotic index, microvessel density (MVD), surface microvessel density (SMD), and DNA ploidy.
- Comparison of these parameters between adenomas treated with bromocriptine (oral/injectable) or quinagolide and untreated adenomas.
Main Results:
- Treated adenomas exhibited significantly lower mitotic and MIB-1 indices compared to untreated ones, indicating reduced cell proliferation.
- MIB-1 labeling significantly decreased with quinagolide treatment.
- Apoptotic indices were not significantly higher in treated adenomas.
- Microvessel density (MVD) was significantly lower in treated adenomas, but surface microvessel density (SMD) showed no significant difference.
- p27 expression was reduced in the bromocriptine long-acting injectable (BEC-LAR) group but not significantly different overall.
- DNA ploidy and other nuclear parameters did not differ significantly between groups.
Conclusions:
- Suppression of cell proliferation, evidenced by decreased mitotic and MIB-1 indices, is a key mechanism for dopamine agonist-induced lactotroph adenoma shrinkage.
- p27 protein expression and apoptosis play minor roles in the involution of these tumors.
- Further research is needed to understand the impact of dopamine agonists on microvessel density (MVD) and surface microvessel density (SMD).
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