Hypothalamic GH receptor gene expression in the rat: effects of altered GH status.
GH synthesis and release from the anterior pituitary is governed by the opposing actions of somatostatin (SS) and GH-releasing factor (GRF), derived from the periventricular and arcuate nucleus (ARC) of the hypothalamus respectively. GH is known to regulate its own release by hypothalamic autofeedback mechanisms, but the extent to which this is a direct effect rather than indirectly via the generation of IGFs is still a subject of debate. GH receptors are known to be present in the hypothalamus, 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, using hypophysectomized normal and dw/dw dwarf rats as models of acquired and congenital GH deficiency. Hypophysectomy resulted in a time-dependent reduction in GH receptor gene expression. ARC GH receptor transcripts in untreated dw/dw dwarf rats were half those found in normal animals 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 200 micrograms human GH (hGH)/day for 6 days increased ARC GH receptor expression in dw/dw rats to normal. In contrast, central infusions of hGH at 26.4 and 79.2 micrograms/day for 6 days in normal rats lowered ARC GH receptor gene expression. The sensitivity of GH receptor gene expression within the central nervous system to peripheral and central GH levels suggests that feedback regulation of GRF and/or SS may be mediated directly by these receptors, and that the sensitivity to GH feedback is also subject to autoregulation by GH altering its own receptor expression.
D000818:Animals; D001483:Base Sequence; D005246:Feedback; D005260:Female; D005786:Gene Expression Regulation; D006130:Growth Disorders / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D007016:Hypophysectomy; D007031:Hypothalamus / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism
D015345:Oligonucleotide Probes; D011986:Receptors, Somatotropin; D013006:Growth Hormone