Effects of Exogenous Glucocorticoid Infusion at Birth on Appetitic Center Brain Development During Early Postnatal Life and Its Impact on Voluntary Feed Intake in Beef Cattle

The objective of study was to determine the effects of exogenous cortisol administration on leptin concentrations relative to 1) appetitic center development of the hypothalamus by gene expression in dairy bull calves and 2) altered voluntary feed intake in beef calves. In experiment 1, Holstein bull calves (n = 27) were weighed and randomly assigned to treatments within four hours of parturition (day 0). Each calf was intravenously infused with either a low cortisol (LC; n = 9, 3.5 ug/kg of body weight (BW)), high cortisol (HC; n = 9, 7.0 ug/kg of BW), or a sham infusion control (CON; n = 9, similar volume of saline). Each calf was administered a second infusion (half dose) of its respective treatment 24 h postpartum. All calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood collections were performed via jugular venipuncture before infusion and daily from days 0-5 of age. At 5 days of age, calves were euthanized via overdose of sodium pentobarbital (Beuthanasia-D Special; Schering-Plough Animal Health, Union, NJ). Cerebral-spinal fluid (CSF) from the third ventricle of the brain, hypothalamic, and adipose tissue (AT; omental, perirenal, and mesenteric) were collected. Blood and CSF samples were analyzed for leptin concentrations via a validated RIA (Multispecies leptin RIA, Linco Research, St. Charles, MO, USA). Adipose tissue samples were analyzed via western blotting for leptin and glucocorticoid receptor (GR) and normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression. Hypothalamus samples were analyzed via qRT-PCR for genes of interest associated with neuronal growth factors and normalized to the average of two housekeeping genes. In experiment 2, calves (n = 32 males; n = 30 females) from Angus and Angus crossbred cows were weighed and randomly assigned to treatments as previously described in experiment 1. Blood collections were performed via jugular venipuncture before infusion and daily from days 0-17 of age. Calves were weaned via abrupt separation from dams at ~7 months of age and BW was collected biweekly from day 0 until the end of the study. Animals entered an automated feeding behavior data acquisition system (GROWSAFE Systems, Airdrie, Alberta, Canada) at 367 ± 4 days of age and 385 ± 4 days for heifers and steers respectively and daily feed intake (FI) calculated. Animals were randomly allotted to one of two pens (per sex) with three nodes per pen and allowed a two week adjustment period to a commercial total mixed ration (1.27 Mcal NEm/kg and 15.8% CP; all on DM basis) for heifers and a finishing ration (1.30 Mcal NEm/kg, 0.45 Mcal NEg/kg and 13.8% CP; all on DM basis) for steers. Heifer body condition scores (BCS) were collected at the beginning and end of the trial. Heifers underwent the feeding trial for 70 days and steers until they obtained a back fat (BF) thickness at the 12th rib of 1.15 cm (~110-140 days). Blood samples were analyzed similar to experiment 1. All data was analyzed via repeated measures using appropriate models of SAS (SAS Institute Inc., Cary, NC). Perinatal dairy bull calves had decreased (P < 0.013) serum and CSF leptin concentrations of HC and LC calves compared to CON whilaye day 0 was decreased (P < 0.001) compared to all other days of age. Leptin protein expression was decreased (P < 0.044) in perirenal and omental AT of LC calves compared to CON. Hypothalamic expression of BDNF, FGF1 and FGF2 were decreased (P<0.006) in HC and LC compared to CON. In postnatal beef calves, a treatment by day interaction (P = 0.0028) was reported in which decreased (P < 0.001) serum leptin concentrations were observed in HC and LC calves compared to CON from days 2-17 of age. Calf BW at birth and adjusted 205d weaning weight did not differ (P > 0.05) between treatments. During the feeding trial: BW gain, BCS change, number of feed events were increased (P = 0.001) in LC compared to HC and CON heifers, while steers BF thickness did not differ between treatments (P > 0.05). However, LC observed greater daily FI (P = 0.047), tended to have greater final BW (P = 0.080), and numerically required fewer days on feed to achieve finishing weight compared to HC and CON steers. In summary, exogenous cortisol administered to calves at birth reduced leptin concentrations and altered appetitic control center development of the brain in perinatal dairy bull calves and improved FI of beef steers during a feeding trial.

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