Histochemical Analysis of Laminin a Chains in Diethylstilbestrol-Induced Prolactinoma in Rats

Laminin, a major basement membrane component, is important in structural support and cell proliferation and differentiation. Its 19 isoforms are assemblies of alpha, beta, and gamma chains, and the alpha chains (alpha 1-5) determine the isoform characteristics. Although our previous studies showed alterations in alpha chain expressions during anterior pituitary development, their expressions in pituitary tumors yet to be determined. The present study used a rat model of diethylstilbestrol (DES)-induced prolactinoma to examine alpha chain expressions during prolactinoma tumorigenesis (0-12 weeks of DES treatment) by in situ hybridization and immunohistochemistry. mRNA of alpha 1, alpha 3, and alpha 4 chains was detected in control and after 4 weeks of DES treatment. These expressions were undetectable after 8 weeks of DES treatment and in prolactinoma (12 weeks of DES treatment). Immunohistochemistry showed that the alpha 1 chain was localized in some anterior pituitary cells in control and after 4 weeks of treatment and in endothelial cells after 8 weeks of treatment. The alpha 3 and alpha 4 chains were expressed in endothelial cells, and immunoreactivity and the number of immunopositive cells decreased during DES treatment. These findings suggest that alteration of laminin alpha chains is related to abnormal cell proliferation and neovascularization during development of DES-induced prolactinoma.