FETAL-SPECIFIC AND TUMOR-SPECIFIC REGULATION OF GROWTH-HORMONE RECEPTOR MESSENGER-RNA EXPRESSION IN HUMAN LIVER

Eight different 5'-untranslated region variants of the human growth ho rmone receptor (hGHR) mRNA have been identified in adult liver (V1-V8) . We have compared the expression of two of these variants (V1 and V3) in several human fetal and postnatal tissues (including liver) as wel l as in hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs). Us ing reverse transcription-PCR assays, followed by Southern blotting to confirm the specificity of the amplified fragments, we found that V3 was expressed in all fetal and postnatal liver (n = 13 fetal and 5 pos tnatal), kidney (n = 4 fetal and 4 postnatal), lung (n = 4 fetal and 2 postnatal), intestine (n = 8 fetal and 4 postnatal), skeletal muscle (rt = 1 fetal and 1 postnatal), and adrenal (n = 1 fetal and 1 postnat al) samples. In contrast, V1 was expressed only in postnatal liver. We then screened for V1 and V3 in HBs (n = 17, ages 6-36 months, includi ng 5 with paired normal liver), and HCCs (n = 4, ages 50-75 years, wit h paired normal liver). V1 was undetectable in 15 of 17 HBs, including all HBs paired with (V1-expressing) normal liver; the absence of V1 d id not correlate with patient age, sex, HE subtype, +/- chemotherapy, exon 3-retaining and -deficient hGHR mRNA isoform pattern, or loss of heterozygosity at lip, Ip, and Iq. The four HCCs showed marked (>20-fo ld; n = 2) or complete (n = 2) suppression of V1 as compared to paired normal liver. V3 was expressed in all HBs, HCCs, and paired normal li vers. Interestingly, V3, but not V1, was detected in two Wilms' tumor and paired normal kidney specimens. Our findings suggest that, in the human, there is tissue-, fetal- and tumor-specific regulation of V1 hG HR mRNA.