Simple SummaryThe profitability of production systems for livestock is directly impacted by body weight, which is influenced by an individual animal’s hypothalamic regulation of food intake. The objective of this study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations, protein expression in various fat depots, and the hypothalamic expression of genes associated with appetite regulation in Holstein bull calves. Within 4 h of parturition, Holstein bull calves (9/treatment) were intravenously infused with either a low (3.5 µg/kg of body weight (BW)) or high (7.0 µg/kg of BW) dose of cortisol or a sham infusion control (with a similar volume of saline). At five days of age, blood, cerebrospinal fluid from the third ventricle of the brain, and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected for the analysis of proteins and genes associated with appetite regulation. Exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and cerebrospinal fluid, decreased the protein expression of leptin in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue. Further investigation is necessary to determine if glucocorticoid administration can be utilized as a tool to improve feed intake in cattle later on in life due to hypothalamic programming at birth.AbstractThe objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC;n= 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC;n= 9, 7.0 µg/kg BW), or control (CON;n= 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum (p= 0.013) and CSF (p= 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased (p< 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased (p< 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.