Hyperprolactinemia and pituitary enlargement in Drd2–/– and Prlr–/– mice. Serum PRL increased with age in both female (a) and male (b) Drd2–/– and Prlr–/– mice and was more marked in Prlr–/– mice. Deficiency of both receptors produced an additive effect on hyperprolactinemia in male mice. Prlr–/– mice of both sexes developed hyperprolactinemia at younger ages than did Drd2–/– mice. P < 0.005 for ANOVA of main effect of genotype at all timepoints. *P < 0.05 for pairwise comparisons by the Fisher post hoc test. n = 6–22 for ages 8 weeks and 6 months, and n = 4–8 for ages 12 months and older. (c) Female Drd2–/– mice and Prlr–/– mice had slightly enlarged pituitary glands at 6 months and massively enlarged glands at 14 months (10- to 20-fold greater than wild-type). (d) Moderate pituitary enlargement occurred only at 18–21 months in Prlr–/– and compound homozygous mutant male mice. P < 0.001 for ANOVA of main effect of genotype for females at 14 months and males at 18–21 months. *P < 0.05 for pairwise comparisons using the Fisher post hoc test; n = 3–4 for 6-month-old females and 12-month-old males (except n = 1 for Prlr–/– male and n = 2 for Drd2–/– males); n = 5–7 for 14-month-old females and 18- to 21-month-old males.