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), w hich 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, GHR(1), has recently been shown to be liver specific and found at higher levels in females. We have measured the h epatic GHR(1), GHR, and GHBP transcript levels, by RNase protection an d solution hybridization assay, in animals with differing hormonal sta tus, in which hepatic GHR binding and plasma GHBP have been previously assayed. Estradiol (E(2)) induced GHR(1) in males, whereas ovariectom y or the antiestrogen tamoxifen reduced GHR(1) expression in females. The induction of GHR(1) by E(2) was GH dependent, being lower in GH-de ficient dwarf rats and absent in hypophysectomized rats, paralleling p revious measurements of plasma GHBP and hepatic GHR binding in these a nimals. Significant changes in GHR(1) could explain the trends seen in the same extracts when coding region probes were used. Short-term adr enalectomy had no effect on GHR and GHBP expression, but dexamethasone markedly reduced both protein and messenger RNA (mRNA) levels. Cortic osterone treatment had no effect alone but reduced the E(2)-induced in crease in GHR(1) levels, whereas methylprednisolone administered orall y reduced hepatic GH binding, plasma GHBP, and GHR(1) mRNA levels. Thu s, 5'-UTRs, encoded by different first exons, are involved in the regu lation of hepatic GHR and GHBP expression and need to be considered wh en comparing effects of hormonal manipulation on the mRNA transcripts and protein products of the GHR gene. Previous studies have found disc repancies between levels of protein expression and mRNA transcripts me asured only with coding region probes. Our results suggest that posttr anscriptional differences related to 5'-UTR heterogeneity in the GHR g ene explain some of these discrepancies.