HYPOTHALAMIC DOPAMINERGIC-NEURONS IN PROLACTIN-DEFICIENT AMES DWARF MICE - LOCALIZATION AND QUANTIFICATION OF DEFICIT BY TYROSINE-HYDROXYLASE IMMUNOCYTOCHEMISTRY

Hypothalamic tuberoinfundibular prolactin-inhibiting neurons show decr eased levels and synthesis of dopamine in two types of genetically pro lactin-deficient dwarf mice (Snell, Ames) which arise from separate mu tations. A reduction to 2% of normal in this neuronal population has b een quantified for Snell dwarfs. The present study was undertaken in o rder to quantify morphometrically the deficit and its distribution in Ames dwarf mice, including comparisons of sex and adult age. The brain s of dwarf (df/df) and normal phenotypic (DF/?) sibling mice of both s exes from 4 to 16 months of age were immunostained for tyrosine hydrox ylase, the rate-limiting enzyme in dopamine synthesis; neuronal perika rya were counted in coronal sections of tuberoinfundibular arcuate nuc leus (area A12), medial zona incerta (A13) and anterior periventricula r (A14) hypothalamic areas at 180 mu m rostral-to-caudal intervals. No rmal (DF/?) mice exhibited no differences in neuron numbers, with rega rd to age or sex, in any of the three dopaminergic areas. In dwarf mic e, a tendency toward decreased neuron numbers with age was statistical ly significant for area A14 only, and the size of the neuronal populat ion in A12 was reduced in males compared with females. Total A12 neuro n number in dwarfs was 48% of that in normal mice (P <0.001). Perivent ricular (A14) perikaryal numbers were reduced slightly (P<0.05) in dwa rfs 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 num ber 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 mu m sampling interval. Thus, lifelong absence of prolacti n in Ames dwarf mice is accompanied by a significant decrease in hypot halamic tyrosine hydroxylase-immunoreactive neurons, which is restrict ed to hypophysiotropic areas, uniformly distributed within A12, and is less severe than the reduction in the phenotypically similar Snell dw arf.