HYPOTHALAMIC GH RECEPTOR GENE-EXPRESSION IN THE RAT - EFFECTS OF ALTERED GH STATUS

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.