Postnatal reduction in number of hypothalamic tuberoinfundibular dopaminergic neurons in prolactin-deficient dwarf...

Mice homozygous for the recessive 'Ames' dwarf mutation have undetectable serum or pituitary prolactin (PRL). Accompanying this pituitary deficiency is a marked reduction of dopamine (DA) and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH) in PRL-regulating tuberoinfundibular hypothalamic neurons. In order to determine whether this deficit in adult Ames dwarf mice is congenital or arises postnatally, brains of dwarf (df/df) and normal (DF/?) littermate mice were assessed for TH immunoreactivity from 7 days through 2 months of age. Numbers of TH-positive neurons were counted in three hypothalamic DA areas: tuberoinfundibular A12, medial zona incerta A13, and anterior periventricular A14. There was an increase in the number of TH-positive neurons between 7 and 21 days of age in A12 and A14, but not in A13, for both DF/? and df/df mice. Between 21 days and 2 months of age, cell numbers were the same in all three areas in DF/? mice and in A13 and A14 in df/df mice. However, A12 TH-positive cell number in dwarfs decreased significantly (p < 0.01) between 21 days and 2 months, and was markedly lower (p < 0.001) in df/df than in DF/? mice at 2 months of age. The results emphasize the specificity of the dopaminergic neuron reduction in the Ames dwarf, which is restricted to the PRL-regulating tuberoinfundibular region. The data also indicate that the dwarf DA/TH deficit has an onset in late postnatal development, suggesting a response to absence of target PRL, rather than a primary hypothalamic effect of the dwarf mutation.