DEVELOPMENTAL ASSESSMENT OF HYPOTHALAMIC TUBEROINFUNDIBULAR DOPAMINE IN PROLACTIN-DEFICIENT DWARF MICE

Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by vis ualization using formaldehyde-induced catecholamine histofluorescence and by quantification using catecholamine HPLC at selected postnatal a ges (7, 14, 21, 30, and 90 days). Phenotypically normal (DF/?) litterm ate mice were compared with dwarfs by both methods at each age. The st udies were designed to investigate whether the known deficiency in hyp othalamic tuberoinfundibular DA in adult dwarfs is present neonatally or develops over the postnatal period. The anterior pituitary of each mouse was processed for GH and PRL immunocytochemistry. At 7 days of a ge, GH immunostaining was robust, and scattered PRL-positive cells wer e noted in DF/? pituitary. Homogenously distributed PRL cells increase d in number through 30 days of age in normal mice. Neither GH nor PRL immunoreactivity was present in df/df mice at any age. At 7, 14, and 2 1 days of age, hypothalamic DA tuberoinfundibular histofluorescence wa s comparable in df/ff and DF/? mice. At 90 days of age, tuberoinfundib ular histofluorescence in normal mice remained intense, but was virtua lly undetectable in dwarfs. The developmental change affected only tub eroinfundibular neurons, since DA histofluorescence in nonhypophysiotr opic areas, such as substantia nigra (SN), was qualitatively comparabl e for df/df and DF/? for all ages examined. Norepinephrine (NE) fluore scence in hypothalamus was also comparable for df/df and DF/?. Catecho lamine HPLC provided quantitative confirmation of histofluorescence ob servations. DA and NE levels in both hypothalamus and ventral midbrain , including SN, increased during development in both df/df and DF/? br ains. NE levels were not different between dwarf and normal animals at any age in either medial basal hypothalamus (MBH) or SN. The DA conce ntration in SN was not different between df/df and DF/? at any age exa mined. MBH DA was comparable in df/df and DF/? mice at 7, 14, and 21 d ays of age; at 30 and 90 days, MBH DA was markedly lower (P < 0.001) i n dwarf than in normal mice. Although MBH DA in dwarfs was comparable to that in normal mice at 21 days, the increase in dwarfs between 14 a nd 21 days was not statistically significant. Thus, the hypothalamic D A deficit that exists in adult dwarf mice is not present neonatally an d represents a failure to increase DA compared with normal mice after 14 days of age. The failure of continued development of hypophysiotrop ic tuberoinfundibular DA neurons in dwarf mice is correlated chronolog ically with absent pituitary PRL production.