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Bone morphogenetic protein-4 control of pituitary pathophysiology
Damiana Giacomini1, Marcelo Páez-Pereda, Marily Theodoropoulou
1Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina.
Frontiers of Hormone Research
|July 1, 2006
Summary
Bone morphogenetic protein-4 (BMP-4) plays a dual role in pituitary adenomas, promoting some while inhibiting others. Its interaction with retinoic acid offers a potential therapeutic target for Cushing disease.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor-Beta (TGF-Beta) family, is implicated in pituitary adenoma development.
- Overexpression of BMP-4 is observed in prolactinoma models, potentially driving adenoma progression.
- SMAD proteins, activated by TGF-Beta and BMP family growth factors, interact with estrogen receptors, influencing pituitary cell proliferation.
Purpose of the Study:
- To review the complex and opposing roles of BMP-4 in the progression of various pituitary adenomas.
- To explore the potential of the BMP-4 and retinoic acid interaction as a therapeutic strategy for Cushing disease.
Main Methods:
- Review of existing literature on BMP-4 expression and function in pituitary adenomas.
- Analysis of the interaction between BMP-4, SMAD proteins, and estrogen receptors in pituitary cell proliferation.
- Investigation of BMP-4's role in corticotropinoma cell proliferation and its mediation of retinoic acid's antiproliferative effects.
Main Results:
- BMP-4 is overexpressed in prolactinoma models, contributing to adenoma development.
- BMP-4 exhibits differential expression in normal and adenomatous corticotropes, with an inhibitory effect on corticotropinoma cell proliferation.
- BMP-4 mediates the antiproliferative effects of retinoic acid in corticotropinoma cells.
Conclusions:
- BMP-4 plays a critical and dichotomous role in pituitary adenoma progression.
- The interplay between BMP-4 and retinoic acid presents a promising novel therapeutic target for Cushing disease.
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