Hypothalamic Dopaminergic Neurons in Prolactin‐Deficient Ames Dwarf Mice: Localization and Quantification of Deficit by Tyrosine Hydroxylase Immunocytochemistry

Hypothalamic tuberoinfundibular prolactin‐inhibiting neurons show decreased levels and synthesis of dopamine in two types of genetically prolactin‐deficient dwarf mice (Snell, Ames) which arise from separate mutations. A reduction to 2% of normal in this neuronal population has been quantified for Snell dwarfs. The present study was undertaken in order to quantify morphometrically the deficit and its distribution in Ames dwarf mice, including comparisons of sex and adult age. The brains of dwarf (df/df) and normal phenotypic (DF/?) sibling mice of both sexes from 4 to 16 months of age were immunostained for tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis; neuronal perikarya were counted in coronal sections of tuberoinfundibular arcuate nucleus (area A12), medial zona incerta (A13) and anterior periventricular (A14) hypothalamic areas at 180 μm rostral‐to‐caudal intervals. Normal (DF/?) mice exhibited no differences in neuron numbers, with regard to age or sex, in any of the three dopaminergic areas. In dwarf mice, a tendency toward decreased neuron numbers with age was statistically significant for area A14 only, and the size of the neuronal population in A12 was reduced in males compared with females. Total A12 neuron number in dwarfs was 48% of that in normal mice (P< 0.001). Periventricular (A14) perikaryal numbers were reduced slightly (P<0.05) in dwarfs compared with normals. Numbers of A13 neurons were comparable for DF/? and df/df. The morphometric distribution of tyrosine hydroxylase‐immunoreactive neurons in A12 showed that the decrease in neuronal number in dwarfs was distributed throughout the rostral‐to‐caudal length of the nucleus, with significant decrease of total perikarya (P<0.05) at each 180 μm sampling interval. Thus, lifelong absence of prolactin in Ames dwarf mice is accompanied by a significant decrease in hypothalamic tyrosine hydroxylase‐immunoreactive neurons, which is restricted to hypophysiotropic areas, uniformly distributed within A12, and is less severe than the reduction in the phenotypically similar Snell dwarf.