Steroid regulation of growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids in the rat.
In the rat, the GH receptor (GHR) and the GH-binding protein (GHBP), which arise from alternative splicing of the same gene, show a sexually dimorphic and GH-dependent expression pattern. Multiple alternative 5'-untranslated regions (UTRs) are present in GHR and GHBP transcripts in the rat, one of which, GHR1, has recently been shown to be liver specific and found at higher levels in females. We have measured the hepatic GHR1, GHR, and GHBP transcript levels, by RNase protection and solution hybridization assay, in animals with differing hormonal status, in which hepatic GHR binding and plasma GHBP have been previously assayed. Estradiol (E2) induced GHR1 in males, whereas ovariectomy or the antiestrogen tamoxifen reduced GHR1 expression in females. The induction of GHR1 by E2 was GH dependent, being lower in GH-deficient dwarf rats and absent in hypophysectomized rats, paralleling previous measurements of plasma GHBP and hepatic GHR binding in these animals. Significant changes in GHR1 could explain the trends seen in the same extracts when coding region probes were used. Short-term adrenalectomy had no effect on GHR and GHBP expression, but dexamethasone markedly reduced both protein and messenger RNA (mRNA) levels. Corticosterone treatment had no effect alone but reduced the E2-induced increase in GHR1 levels, whereas methylprednisolone administered orally reduced hepatic GH binding, plasma GHBP, and GHR1 mRNA levels. Thus, 5'-UTRs, encoded by different first exons, are involved in the regulation of hepatic GHR and GHBP expression and need to be considered when comparing effects of hormonal manipulation on the mRNA transcripts and protein products of the GHR gene. Previous studies have found discrepancies between levels of protein expression and mRNA transcripts measured only with coding region probes. Our results suggest that posttranscriptional differences related to 5'-UTR heterogeneity in the GHR gene explain some of these discrepancies.
Gabrielsson
B G
BG
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, London, United Kingdom.
Carmignac
D F
DF
Flavell
D M
DM
Robinson
I C
IC
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013256:Steroids; D013739:Testosterone; D004958:Estradiol; D013006:Growth Hormone; C051815:somatotropin-binding protein