Growth hormone plays a central role in the change in nutrient metabolism that occurs during the initiation of lactation. The actions of growth hormone are mediated by the growth hormone receptor (GHR) whose mRNA is present in three alternatively spliced forms (GHR 1A, 1B, and 1C). Liver-specific GHR 1A mRNA is transiently decreased around parturition, but the exact timing of the decline is not known. Our objective was to generate a daily profile for total GHR (GHRtot; all GHR transcripts), GHR 1A, and IGF-I mRNA expression in liver of periparturient Holstein cows and evaluate these daily mRNA profiles relative to daily profiles for periparturient hormones and metabolites. Liver biopsies and blood samples (n = 139) were collected from 65 Holstein cows at the University of Missouri Dairy Farm. At least two cows were sampled on each day from 14 d before to 14 d after parturition. Total cellular RNA was isolated and reverse transcribed to cDNA. Target cDNA were measured by quantitative real-time polymerase chain reaction. Plasma was assayed for progesterone, estradiol, insulin, growth hormone, IGF-I, glucose, and nonesterified fatty acids. The GHR 1A mRNA declined 2 d before parturition, was lowest 3 to 4 d after parturition, and then increased. The IGF-I mRNA declined 1 d after parturition, was lowest 2 to 5 d after parturition and then increased. Total GHR mRNA was not affected by day. The decrease in GHR 1A mRNA was associated with a decrease in progesterone and an increase in estradiol shortly before parturition. A detailed profile of GHR 1A, IGF-I, and GHRtot mRNA expression during the periparturient period was provided. The decreases in GHR 1A and IGF-I during the transition period occurred immediately before (GHR 1A) or shortly after (IGF-I) parturition. Rapid changes in placental and ovarian steroids before parturition were coincident with changes in GHR 1A mRNA.

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 (Bmax) 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.

Uncoupling of the growth hormone (GH) axis in early postpartum dairy cows is correlated with a decrease in liver GH receptor (GHR) 1A mRNA and a decrease in liver GH receptor protein. Postpartum recoupling of the GH axis is also correlated with GHR 1A mRNA and GHR protein. We hypothesized that dry matter intake (DMI) partially controls the increase in GHR 1A mRNA postpartum. Prepartum Holstein dairy cows (n = 11) were offered feed ad libitum. After calving, 6 cows were fed 70% of their expected DMI (feed restriction) for 14 d and 5 cows were fed ad libitum (control). Both groups were fed ad libitum after d 14. Liver was biopsied prepartum and on d 1, 7, 14, and 21 postpartum; blood was sampled throughout the experimental period. Rate of increase in postpartum milk production was less for feed-restricted cows. The GHR 1A mRNA decreased from prepartum to d 1 postpartum and subsequently increased. Rate of postpartum increase in GHR 1A mRNA was less in feed-restricted cows. Diminished GHR 1A persisted for at least 7 d after feed-restricted cows returned to ad libitum feeding. Liver insulin-like growth factor-I mRNA concentrations decreased from prepartum to d 1 as well, but were similar for feed restricted and control thereafter. We concluded that DMI partially controls GHR 1A mRNA expression in early postpartum dairy cows and that the decrease in GHR 1A in response to feed restriction persisted for at least 1 wk after ad libitum feeding was restored.

The weaning to estrus and weaning to ovulation intervals in sows are controlled by ovarian follicular growth after weaning. Longer intervals could be caused by smaller diameter follicles at weaning that take more time to reach a preovulatory size. We addressed this hypothesis by decreasing the diameter of follicular populations before weaning and then measuring follicular development and interval to estrus and ovulation after weaning. The posterior vena cava, cranial to the entry of the ovarian vein, was cathetered for blood sampling and infusion in 20 sows at 12 +/- 1 d after farrowing. Sows were assigned randomly to receive either 30 mL of charcoal-treated follicular fluid (FF, n = 9; a treatment known to decrease serum FSH and follicular diameter) or 30 mL of saline (n = 11) by venous infusion thrice daily (0700, 1500, and 2300 h) for 96 h beginning at 14 +/- 1 d after farrowing. Sows were weaned 48 h after the last infusion. Blood samples were collected for FSH analysis thrice daily beginning on the day of catheterization and continuing until ovulation. Follicular diameter was determined once daily by transrectal ultrasonography. A treatment x time interaction was detected for serum FSH (P < 0.001) and follicular diameter (P < 0.001) because serum FSH and the diameter of follicular populations decreased in FF sows during the infusion period. After the infusion period, serum FSH rebounded in FF sows, and follicles resumed growth but grew at the same rate as those of saline-treated sows, thus failing to achieve equivalent diameters relative to saline-treated sows on a given day after weaning. As a result, sows treated with FF had longer (P < 0.05) weaning to estrus (6.1 +/- 0.4 d) and weaning to ovulation (8.6 +/- 0.5 d) intervals compared with saline-treated sows (4.7 +/- 0.4 d and 7.2 +/- 0.4 d, respectively). We conclude that the diameter of the follicular population at weaning is one factor that controls interval to estrus and ovulation in sows. Small follicles at weaning cannot undergo compensatory growth and require additional time to reach a preovulatory size.

Growth hormone receptor (GHR) and insulin-like growth factor-I (IGF-I) mRNA decrease in the liver of dairy cows at parturition. Epinephrine is released and feed intake is decreased at the same time. The objective of this study was to determine whether feed restriction and (or) administration of epinephrine could recapitulate the changes in the hepatic GHR 1A and IGF-I mRNA that occur at parturition. Eight lactating cows were randomly assigned to one of two rations (ad libitum or restricted). The cows assigned to the restricted ration were fed 75, 60, 60, and 25% of feed consumed by the ad libitum cows on successive days to mimic the changes in feed intake around parturition. Liver samples were collected by needle biopsy before and after feed restriction. Cows received either 0.02 mg/kg of epinephrine or saline approximately 24 h before the second liver biopsy so that a 2 x 2 factorial arrangement of treatments was created. Feed restriction increased plasma nonesterified fatty acids and liver triglyceride percentages and decreased plasma IGF-I concentrations. The decrease in plasma IGF-I after feed restriction was associated with a decrease in IGF-I mRNA in feed-restricted cows. The amount of GHR 1A mRNA did not change after feed restriction. Epinephrine treatment did not affect the amount of GHR 1A or IGF-I mRNA. We conclude that the decrease in feed intake at parturition may be partially responsible for the decrease in IGF-I but may not cause the decrease in GHR 1A.