PROLACTIN REPLACEMENT DURING DEVELOPMENT PREVENTS THE DOPAMINERGIC DEFICIT IN HYPOTHALAMIC ARCUATE NUCLEUS IN PROLACTIN-DEPENDENT AMES DWARF MICE

PRL-deficient dwarf mice exhibit marked reduction in dopamine (DA) and in tyrosine hydroxylase (TH) immunoreactivity in the PRL-regulating n eurons of the hypothalamic arcuate nucleus (catecholaminergic area A12 ). Recent studies in this laboratory have revealed that this condition develops postnatally, in that A12 DA fails to increase and the number of TH-positive cells decreases after 21 days of age. The present stud y was designed to test whether PRL replacement during the early postna tal period would increase DA and TH expression in dwarfs. Ames dwarf ( df/df) and normal sibling (DF/?) mice were treated with daily injectio ns of ovine PRL (50 gg, ip) or vehicle for 30 days starting on postnat al day 12. Brains were evaluated by catecholamine histofluorescence an d TH immunocytochemistry at the end of the treatment period. TH-positi ve cells were counted in A12 and medial zona incerta (area A13) and al so differentially within A12, in dorsal and ventral regions, and at an terior, middle, and posterior levels. Histofluorescence and TH-positiv e cell number (P < 0.01) in vehicle-treated dwarfs were greatly reduce d compared with those in DF/? mice in A12, but not in A13. However, A1 2 fluorescence in PRL-treated dwarfs was comparable to that in DF/? mi ce. TH cell counts in A12 of PRL-treated dwarfs were significantly hig her (P < 0.01) than those in vehicle-treated dwarfs and not different from those in either group of DF/? mice. Within A12, both dorsal and v entral TH cell numbers were reduced in vehicle-treated dwarfs (P < 0.0 1); the reduction was greater in the ventral subpopulation (P < 0.01). TH cell counts were lower in middle and posterior (P < 0.05), but not anterior, areas of A12 in vehicle-treated df/df mice compared with th ose in DF/? mice. TH cell numbers in all A12 regions in PRL-treated dw arfs were not different from those in DF/? mice. Thus, PRL replacement initiated before 2 weeks of age in dwarfs is effective in supporting DA and TH expression in both A12 neurons and median eminence external zone at normal levels, providing direct evidence that the DA/TH defici t in dwarfs is secondary to endogenous PRL deficiency.