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Pattern of FGF-2 isoform expression correlated with its biological action in experimental prolactinomas

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Abstract

Fibroblast growth factor-2 (FGF-2) synthesized in the pituitary is involved in the formation and progression of pituitary tumors. The aim of this study was to analyze the pattern expression of two FGF-2 isoforms at different subcellular levels and to determine its correlation with prolactinoma development. Estrogen administration to male rats for 7, 20, and 60 days generated pituitary tumors, with lactotrophs being the prevalent cell type. Ultrastructural immunolabeling showed FGF-2 in the cytosolic and nuclear compartments of somatotrophs, lactotrophs and gonadotrophs, as well as in folliculo-stellate cells of normal rats. Estrogen stimulation increased FGF-2 immunoreactivity in various tumors and enhanced the expression of two FGF-2 isoforms, 18 and 22 kDa, as quantified by western blot. The 18 kDa isoform observed in cytosol extracts reached the highest levels after 60 days of hormonal stimulation and this was related to lactotroph proliferation. However, the 22 kDa FGF-2 isoform was only detected in the nuclear compartment and achieved the maximum expression at 7 days of estrogen treatment, without any correlation with lactotroph proliferation. These results suggest that the 18 kDa FGF-2 may play a role in the modulation of lactotroph proliferation in prolactinomas induced by estrogen. The overproduction of both FGF-2 isoforms appears to be implicated in autocrine–paracrine–intracrine mitogenic loops; this FGF-2 activity could lead to uncontrolled cell growth, angiogenesis, and tumor formation.

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Acknowledgements

We are especially grateful to Professor Dr. Sylvia L. Asa from the Department of Laboratory Medicine and Pathobiology, University of Toronto for her critical review of the manuscript. The technical assistance of Mrs Mercedes Guevara and Biochem. Félix D. Roth is gratefully acknowledged. Finally, we would like to thank native speaker Dr Paul Hobson for revising the English of the manuscript. This work was supported by grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT).

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Authors and Affiliations

  1. Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Haya de la Torre, esquina Enrique Barros, Pabellón de Biología Celular, Ciudad Universitaria, X5000, HRA, Córdoba, Argentina

    Jorge H. Mukdsi, Ana Louis De Paul, Juan P. Petiti, Silvina Gutiérrez, Agustín Aoki & Alicia I. Torres

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  1. Jorge H. Mukdsi
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  2. Ana Louis De Paul
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  3. Juan P. Petiti
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  6. Alicia I. Torres
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Correspondence to Alicia I. Torres.

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Mukdsi, J.H., De Paul, A.L., Petiti, J.P. et al. Pattern of FGF-2 isoform expression correlated with its biological action in experimental prolactinomas. Acta Neuropathol 112, 491–501 (2006). https://doi.org/10.1007/s00401-006-0101-9

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