Growth hormone (GH) binding and expression of GH receptor 1A mRNA in hepatic tissue of periparturient dairy cows

Growth hormone (GH) plays a role in metabolic adaptations that occur during lactogenesis. Liver GH receptor transcript (GHR 1A) is transiently decreased near parturition and may reduce GH-dependent signaling leading to low blood insulin-like growth factor I (IGF-I) concentrations in periparturient dairy cattle. We hypothesized that the decrease in GHR 1A mRNA at parturition was associated with decreased GH binding (i.e., GHR protein concentration) in liver. Blood and liver biopsy samples were collected from 12 Holstein cows on d -12 ± 1, 3, and 17 relative to parturition. Total cellular RNA was isolated from a sub-sample of liver. Quantitative real-time polymerase chain reactions were used to measure GHR 1A, total GHR, IGF-I, and cyclophilin mRNA. Microsomal membranes were isolated from the remaining liver tissue and assayed for ¹²⁵I-bGH binding. Plasma was assayed for GH and IGF-I concentrations. Liver GHR 1A mRNA, specific ¹²⁵I-bGH binding to liver membranes, liver IGF-I mRNA, and plasma IGF-I concentrations were lower on d 3 relative to d -12. The GHR 1A mRNA, ¹²⁵I-bGH binding, and plasma GH concentrations increased on d 17 but liver IGF-I mRNA and plasma IGF-I concentrations did not change between d 3 and 17. Total GHR mRNA and cyclophilin mRNA amounts were similar on d -12, 3, and 17. Across all days, ¹²⁵I-bGH specific binding in liver was highly correlated with liver GHR 1A mRNA (R² = 0.68) but not with total GHR mRNA. Saturation binding analysis showed that GHR concentration (B_max) in liver on d 3 had decreased to only 5% of the amount on d -12. We conclude that decreased GHR 1A mRNA leads to decreased GHR protein concentration in liver. Reduced GHR in liver likely contributes to a decrease in liver IGF-I production and reduced concentrations of IGF-I in blood of periparturient cows.