Gb. Thomas et al., Differential regulation of hypothalamic tuberoinfundibular dopamine neurones in two dwarf rat models with contrasting changes in pituitary prolactin, J NEUROENDO, 11(3), 1999, pp. 229-236
In transgenic growth-retarded (Tgr) rats, expression of human growth hormon
e (hGH) is targeted to hypothalamic GH-releasing hormone (GHRH) neurones. I
n these rats, GHRH is reduced and somatostatin expression is increased, res
ulting in secondary GH deficiency and dwarfism. Tgr rats also show reduced
pituitary prolactin (PRL), which may reflect an additional lactogenic feedb
ack action of the hGH transgene, analogous to that in mice transgenic for p
eripheral hGH which show enhanced dopamine (DA) and tyrosine hydroxylase (T
H) expression in the hypothalamic tuberoinfundibular dopaminergic (TIDA) ne
urones that inhibit PRL secretion. The present study examined DA histofluor
escence and TH immunoreactivity in Tgr rats, and also in dw/dw rats, a dwar
f strain with primary pituitary GH but not PRL deficiency. Radioimmunoassay
confirmed a significant decrease in total pituitary PRL content in Tgr rat
s, but showed a marked increase in total pituitary PRL in dw/dw rats. Despi
te their PRL deficiency, Tgr rats showed qualitatively increased TIDA histo
fluorescence and TH immunoreactivity compared with AS control rats, though
the total number of detectable TH-positive TIDA neurones was similar for Tg
r and AS. In contrast, dw/dw rats showed increased numbers of TH-immunoreac
tive TIDA neurones whilst TIDA fluorescence was unchanged, and these findin
gs were not affected in dw/dw rats given bovine GH (200 mu g/d s.c. for 7 d
). These results suggest that reduced PRL in Tgr rats is due to a local lac
togenic feedback effect of hGH to stimulate TIDA neurones. The complex chan
ges in TIDA neurones probably reflect a combination of increased lactogenic
feedback in Tgr rats, with an increased (Tgr) or decreased (dw/dw) somatog
enic feedback on GHRH neurones, some of which coexpress TH. Thus, the uncha
nged number of TIDA neurones in Tgr rats may result from hGH stimulation of
TH and DA, but a reduction in GHRH-producing cells, whereas increased TIDA
neurones in dw/dw rats suggests a stimulation by endogenous PRL with an in
creased GHRH cell complement due to GH deficiency. These findings therefore
indicate that differences in lactogenic feedback in these dwarf rat models
are reflected in marked differences in their hypothalamic TIDA neurones.