DIFFERENTIAL REGULATION OF THE GROWTH-HORMONE RECEPTOR GENE - EFFECTSOF DEXAMETHASONE AND ESTRADIOL

GH receptor (GHR) expression differs during development between centra l and peripheral tissues. Peripheral GHR expression is known to be sen sitive to gonadal and adrenal steroids, but little is known about thei r effects on GHR in the central nervous system. We have now studied th e effects of estradiol (E(2)) or dexamethasone on GHR expression in ra t arcuate nucleus (ARC) and hippocampus, using quantitative in situ hy bridization. Dexamethasone, which strongly down-regulates hepatic GHR expression, had no effect on central GHR transcript abundance, whereas E(2) treatment, which stimulates hepatic GHR expression, significantl y reduced ARC GHR messenger RNA (mRNA) levels. E(2) also increased som atostatin (SS) expression significantly in both ARC and periventricula r nuclei but did not reduce ARC GH-releasing hormone (GHRH) mRNA level s. Ovariectomy stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS expression. E(2) replacement in ovariectomized anim als restored GHRH and SS mRNA levels to control values. Hippocampal GH R mRNA transcripts showed the same response to these endocrine manipul ations as seen in the ARC. The induction of hepatic GHR expression by E(2) is known to involve the transcription of an alternate 5' untransl ated first exon, GHR(1). This was readily detect able in the liver usi ng a specific GHR(1) probe but could not be detected in any CNS area. Our results show that GHR expression in the CNS is sensitive to regula tion by peripheral steroids but that CNS and hepatic expression of GHR is differentially regulated by the same treatments.