The double mutant (D2R−/−, PRLR−/−) mice used to bypass the short loop feedback and investigate possible dopamine-independent effects of PRL on lactotroph function, exhibited prolactinomas that were significantly larger than those observed in D2R −/− mice [52] However, PRLR−/− mice presented more profound hyperprolactinemia and larger tumours than age-matched D2R −/− mice [52]. This evidence concerns the gene PRL and hyperprolactinemia.