Reduced growth hormone receptor (GHR) messenger ribonucleic acid in liver of periparturient cattle is caused by a specific down-regulation of GHR 1A that is associated with decreased insulin-like growth factor I

GH receptor (GHR) messenger RNA (mRNA) is transcribed from at least three d ifferent promoters within the liver of cattle. The first promoter (P1) is l iver specific and alternatively splices exon 1A onto the GHR mRNA (GHR 1A m RNA). The second and third promoters (P2 and P3) have constitutive activity in many tissues and alternatively splice exons 1B and 1C onto the GHR mRNA (GHR 1B and GHR 1C mRNA). The total amount of GHR in the liver partially d etermines liver insulin-like growth factor I (IGF-I) synthesis in response to GH. Two studies were conducted to characterize the changes in GHR 1A mRN A, alternatively spliced GHR mRNA, and IGF-I mRNA during late pregnancy and early lactation in dairy cattle. Liver RNA was isolated from pregnant Hols tein cattle (Bos taurus) on days -14, 0, and 21 relative to parturition (st udy 1) or days -14, 0, 15, 30, 60, and 90 relative to parturition (study 2) . Ribonuclease protection assays were used to quantify total GHR (all GHR v ariants) as well as liver-specific GHR 1A and alternatively spliced GHR mRN A. Likewise, total IGF-I as well as alternatively spliced IGF-I mRNA (class 1 and class 2 transcripts) were measured. A decrease in total GHR mRNA at parturition (P < 0.01) was associated with a specific decrease in GHR 1A mR NA (P < 0.001). The amount of alternatively spliced GHR mRNA (including GHR 1B and GHR 1C mRNA) did not change at parturition (P > 0.10). Total liver IGF-I mRNA and blood IGF-I concentrations were also decreased at parturitio n (P < 0.05 and P < 0.01, respectively). However, a decrease in IGF-I mRNA was observed for both class 1 and class 2 IGF-I transcripts (P < 0.01 and P < 0.05, respectively). We conclude that the reduced amount of GHR mRNA dur ing early lactation is caused by a specific down-regulation of GHR 1A mRNA that was associated with decreased Liver IGF-I mRNA and decreased blood IGF -I concentrations. These data provide evidence for independent regulation o f GHR mRNA by mechanisms that discriminate between GHR P1 (transcribes GHR 1A) and alternative promoters that transcribe constitutive GHR mRNA.