Prolactin replacement during development prevents the dopaminergic deficit in hypothalamic arcuate nucleus in...

PRL-deficient dwarf mice exhibit marked reduction in dopamine (DA) and in tyrosine hydroxylase (TH) immunoreactivity in the PRL-regulating neurons 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 study was designed to test whether PRL replacement during the early postnatal period would increase DA and TH expression in dwarfs. Ames dwarf (df/df) and normal sibling (DF/?) mice were treated with daily injections of ovine PRL (50 micrograms, ip) or vehicle for 30 days starting on postnatal day 12. Brains were evaluated by catecholamine histofluorescence and TH immunocytochemistry at the end of the treatment period. TH-positive cells were counted in A12 and medial zona incerta (area A13) and also differentially within A12, in dorsal and ventral regions, and at anterior, middle, and posterior levels. Histofluorescence and TH-positive cell number (P < 0.01) in vehicle-treated dwarfs were greatly reduced compared with those in DF/? mice in A12, but not in A13. However, A12 fluorescence in PRL-treated dwarfs was comparable to that in DF/? mice. TH cell counts in A12 of PRL-treated dwarfs were significantly higher (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 ventral TH cell numbers were reduced in vehicle-treated dwarfs (P < 0.01); 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 those in DF/? mice. TH cell numbers in all A12 regions in PRL-treated dwarfs 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 deficit in dwarfs is secondary to endogenous PRL deficiency.