In addition to the well-documented sexual dimorphism in GH secretory pattern in the rat, hepatic GH binding is also different between the sexes with females having two-to threefold more binding than males (43). Levels of circulating GHBP are also higher in female than male rats (24,44,45) although total GHR mRNA levels are not markedly different between the sexes, within the CNS (40), or in liver (13). Nevertheless, there is evidence that the sexual dimorphism also extends to GH feedback because the pituitary responsiveness to GHRH during hGH infusions is markedly different in males and females (46). The authors have shown that GHR expression in the rat CNS is sensitive to regulation by peripheral steroids and that CNS and hepatic expression of GHR are differentially regulated by the same treatments (47). For example, the induction of hepatic GHR expression by estradiol is known to involve the transcription of an alternative 5' untranslated first exon, GHR1 (23). GHR1, although readily detectable in the liver, could not be detected in the CNS (Fig. 4). Estradiol treatment, which stimulates hepatic GHR expression, significantly reduced ARC GHR mRNA levels (Fig. 4). Furthermore, dexamethasone treatment, which profoundly suppressed hepatic GHR transcripts, had no effect on their abundance in the CNS (Fig. 4) (although a decrease has recently been reported ), with a fourfold higher dose of dexamethasone).
Although this differential effect of dexamethasone could be explained by other factors, such as different glucocorticoid receptor expression in liver and brain, it may also be profitable to reinvestigate the effects of these hormones using 5'-specific probes for the other brain variant UTRs, because these could show a similar differential sensitivity for glucocorticoids as they do for estrogen.
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