The dopamine receptor D2 genotype is associated with hyperprolactinemia

A genetic predisposition to hyperprolactinemia is suggested by an excess homozygosity for polymorphism 1 in exon 7 of the DRD2 gene. Previous studies of lactotrophs from prolactinomas have found normal DRD2 receptors but differing isoform density. Homozygosity of polymorphism 1 may influence the distribution of the DRD2 isoforms on the lactotroph. Other potential mechanisms include an association with a molecular defect in a postreceptor signaling mechanism, such as a somatic inactivating mutation in a G1 protein, which could result in autonomous function of the lactotroph. Mutations could also result in different receptor-G protein interactions, such as a Gs instead of Gi, and result in autonomous lactotroph function.