Prolactin replacement in adult dwarf mice does not reverse the deficit in tuberoinfundibular dopaminergic neuron number.

The lack of PRL synthesis in Ames dwarf mice coincides with a marked reduction in dopamine (DA) and in numbers of PRL-inhibiting tuberoinfundibular dopaminergic neurons in the hypothalamus (catecholaminergic area A12), as assessed by tyrosine hydroxylase (TH) immunoreactivity. This DA/TH deficit develops postnatally and can be prevented by PRL replacement initiated at 12 days of age. The present study tested whether a similar PRL treatment in adult dwarfs would reverse the A12 deficit, indicating that these neurons are quiescent due to absent PRL feedback stimulation, or would not reverse the deficit, suggesting that A12 neurons are either absent or refractory to PRL effect. At 60 days of age, Ames dwarf (df/df) mice received renal pituitary allografts from normal (DF/df) donors as a source of mouse PRL. Separate groups of dwarfs were treated sequentially with ovine PRL (50 micrograms/day, ip; 30 days) and vehicle (15 days) to assess whether the putative restorative effect of PRL regressed after hormone withdrawal. Brains were evaluated using DA histofluorescence and TH immunocytochemistry. Total numbers of TH-immunostained cells in A12 and medial zona incerta (area A13) regions were counted, and the intensity of TH immunostaining was assessed by computerized image analysis. The total A12 TH-positive cell number was reduced (P < 0.01) in all PRL-treated dwarfs (1826 +/- 58) compared with that in normal mice (3340 +/- 180), and was not different from that in untreated dwarfs (1953 +/- 304) regardless of the PRL regimen. However, A12 perikarya in all PRL-treated dwarfs showed qualitatively increased histofluorescence and quantitatively increased TH immunostaining (P < 0.01) intensity compared with that in untreated dwarfs, an effect that regressed after ovine PRL withdrawal. Neither cell number nor staining intensity differed by gender. There were no significant differences in A13 cell numbers or staining intensity according to phenotype or PRL treatment. The present results indicate that the tuberoinfundibular dopaminergic neuronal population in adult Ames dwarf mice is permanently reduced, although extant A12 cells in dwarfs are responsive to either homologous or heterologous PRL feedback. Together with the previously reported effect of PRL treatment in neonatal dwarfs, the reduction appears to be the result of absent PRL stimulation during development.