A major regulator of peripheral GHR expression is nutrition, particularly protein malnutrition, which causes a profound fall in GHR expression, GHR binding, and associated GH insensitivity (49,50). A similar situation exists with diabetes (51). So far there is little information about central GHR expression under different planes of nutrition. It may be difficult to interpret studies in the rat in this regard, since this species shows a marked reduction in GH secretion with undernutrition, unlike most other species, which show a rise. The latter might follow from a reduction in central GHR feedback, but could equally well be ascribed to the lack of feedback from IGF-1 under conditions of malnutrition. IGF-1 itself could affect GHR expression, although the effects on peripheral IGF-1 feedback on GH expression are not marked (52) unless coadministered with IGF-2 (53).
GHRs are also regulated by thyroid hormones. The growth-promoting effects of exogenously administered GH are blunted in hypothyroid rats, hepatic GH binding sites are reduced in hypothyroidism, and elevated binding is observed in hyperthyroid rats (54). The authors have recently observed reduced GHR mRNA expression in the ARC in response to thyroidectomy, an effect that is rapidly restored by thyroid hormone replacement (P. A. Bennett, unpublished observations).
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