Pa. Bennett et al., HYPOTHALAMIC GH RECEPTOR GENE-EXPRESSION IN THE RAT - EFFECTS OF ALTERED GH STATUS, Journal of Endocrinology, 147(2), 1995, pp. 225-234
GH synthesis and release from the anterior pituitary is governed by th
e opposing actions of somatostatin (SS) and GH-releasing factor (GRF),
derived from the periventricular and arcuate nucleus (ARC) of the hyp
othalamus respectively. GH is known to regulate its own release by hyp
othalamic autofeedback mechanisms, but the extent to which this isa di
rect effect rather than indirectly via the generation of IGFs is still
a subject of debate. GH receptors are known to be present in the hypo
thalamus, but their physiological regulation is poorly understood. We
therefore used in situ hybridization histochemistry to investigate the
effects of GH status on hypothalamic GH receptor gene expression, usi
ng hypophysectomized normal and dw/dw dwarf rats as models of acquired
and congenital GH deficiency. Hypophysectomy resulted in a time-depen
dent reduction in GH receptor gene expression. ARC GH receptor transcr
ipts in untreated dw/dw dwarf rats were half those found in normal ani
mals of the same background strain (16.8 +/- 1.7 vs 9.3 +/- 1.9 d.p.m.
/mg, P < 0.05). Increasing circulating GH by peripheral infusion of 20
0 mu g human GH (hGH)/day for 6 days increased ARC GH receptor express
ion in dw/dw rats to normal. In contrast, central infusions of hGH at
26.4 and 79.2 mu g/day for 6 days in normal rats lowered ARC GH recept
or gene expression. The sensitivity of GH receptor gene expression wit
hin the central nervous system to peripheral and central GH levels sug
gests that feedback regulation of GRF and/or SS may be mediated direct
ly by these receptors, and that the sensitivity to GH feedback is also
subject to autoregulation by GH altering its own receptor expression.