Natural and molecular history of prolactinoma: insights from a Prlr -/- mouse model. Mus musculus

Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient (Prlr -/-) mouse, in which Prlr -/- females develop large secreting prolactinomas from 12 months of age with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, a highly secreting subtype. Overall design: In order to gain molecular insights into the pathogenesis of prolactinoma in Prlr-/- mice, we performed a microarray analysis at 2 and 4 months of age, before the overt appearance of the tumors. Two and four months-old wild-type (n=6 and 6 respectively) and Prlr KO (n=6 and 6 respectively) mice were sacrified by decapitation. Pituitaries were removed, pooled three by three to form duplicates for each genotype, and frozen at -80°C before RNA extraction and subsequent analysis. The whole experiment was replicated with another set of animals (12 wild-type and 12 Prlr -/- mice) (Note : in the replication experiment (array2), the second duplicate for 4 months-old mice did not hybridize correctly and therefore was removed before analysis, both in the WT and the Prlr KO conditions)