POSTNATAL REDUCTION IN NUMBER OF HYPOTHALAMIC TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS IN PROLACTIN-DEFICIENT DWARF MICE

Mice homozygous for the recessive 'Ames' dwarf mutation have undetecta ble serum or pituitary prolactin (PRL). Accompanying this pituitary de ficiency is a marked reduction of dopamine (DA) and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH) in PRL-regulating tuberoinf undibular hypothalamic neurons. In order to determine whether this def icit in adult Ames dwarf mice is congenital or arises postnatally, bra ins of dwarf (df/df) and normal (DF/?) littermate mice were assessed f or TH immunoreactivity from 7 days through 2 months of age. Numbers of TH-positive neurons were counted in three hypothalamic DA areas: tube roinfundibular A12, medial zona incerta A13, and anterior periventricu lar A14. There was an increase in the number of TH-positive neurons be tween 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 w ere 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 sign ificantly (p<0.01) between 21 days and 2 months, and was markedly lowe r (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 tuberoinfundibu lar 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.