Differential actions of the dopamine agonist bromocriptine on growth of SMtTW tumors exhibiting a prolactin and/or a somatotroph cell phenotype: Relation to dopamine D-2 receptor expression

Dopamine (Da) and Da agonists are known to inhibit secretion and proliferat ion of normal and tumoral PRL cells, through receptors of D-2 subtype. Beca use of the lack of an experimental model, the relationship between bromocri ptine (BR) sensitivity and D-2 receptor expression is poorly documented. Su ch a relationship was analyzed using five lineages of spontaneous transplan table rat pituitary tumors (SMtTW) exhibiting different PRL/GH phenotypes. From plasma PRL and GH concentrations of rats bearing the tumors and tumor messenger RNA contents, tumors were classified as PRL (SMtTW(2)), somatotro ph (SMtTW(10)), or somatomammotroph (SMtTW(5)) tumors. Two lineages (SMtTW( 3) and SMtTW(4)) represented variants producing PRL and GH but with a high predominance of PRL. With the exception of SMtTW(4) tumors, which were mali gnant, all the tumors were benign and differed in their growth rate. Hormon e production and growth of tumors with a PRL or a somatomammotroph phenotyp e were reduced by about 90% under BR treatment, whereas somatotroph tumors and the PRL malignant tumors were totally insensitive to BR. D-2 receptor m essenger RNA was present in all BR-sensitive tumors and was not detected in BR-resistant tumors. In conclusion, using five lineages of SMtTW tumors that are representative of the most frequent tumors encountered in human pituitary pathology, we fo und a full concordance between tumor responses to BR and the expression of D-2 receptor by the tumors. The identification of a tumor lineage with a ma lignant phenotype, secreting high amounts of PRL and presenting a resistanc e to BR, supports the idea that Da-resistant prolactinomas are aggressive t umors.