STIMULATORY EFFECT OF HUMAN, BUT NOT BOVINE, GROWTH-HORMONE EXPRESSION ON NUMBERS OF TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS IN TRANSGENIC MICE

Mice transgenic for heterologous and ectopic GH expression serve as mo dels for studying the feedback effects of elevated nonregulated GH on hypothalamic hypophysiotropic neurons as well as on peripheral functio n. For example, hypothalamic somatostatin expression has been shown to be increased markedly in mice bearing either bovine (b) or human (h) GH transgenes. Human, but not bovine, GH has lactogenic properties in mice, and appears to stimulate PRL-inhibiting tuberoinfundibular dopam inergic (TIDA) neurons. The present study was designed to determine th e effect of a lifelong excess of hGH on dopamine (DA) expression in an d numbers of TIDA neurons. Male mice of four transgenic lines were exa mined. The transgenic animals bore constructs of either bGH or hGH fus ed to either metallothionein (MT) or phosphoenolpyruvate carboxykinase (PEPCK) promoters; brains of transgenic mice were compared morphologi cally with those of nontransgenic littermates. Formaldehyde-induced ca techolamine histofluorescence and tyrosine hydroxylase (TH) immunocyto chemistry were examined in alternate brain sections; cell number was q uantified for TIDA neurons (area A12) and a nonhypophysiotropic dience phalic DA area, the medial zona incerta (A13). Body weights were highe r (P < 0.01) in PEPCK-GH than in MT-GH transgenic mice, as were serum levels of heterologous GH in those lines. In MT-hGH, but not MT-bGH or PEPCK-bGH, transgenic mice, A12 perikaryal fluorescence was enhanced, and ME fluorescence was reduced compared with those in control animal s. The reduced ME DA is likely to reflect stimulation of TIDA neurons, because A12 TH-immunoreactive neuron number was increased by 34% in M T-hGH mice compared with that in controls (P < 0.05). In mice bearing the PEPCK-hGH construct, A12 TH neuron number was increased 47% (P < 0 .001) compared with that in littermate controls. There were no differe nces in A13 cell number among animals, and A12 cell numbers in mice ex pressing bGH did not differ from control values. These results suggest that although extremely high levels of circulating bGH do not stimula te TIDA neurons, lifelong high levels of hGH have a stimulatory and gr aded effect on developmental differentiation of these cells for TH and DA production, supporting the concept of PRL as a trophic factor for TIDA neurons.