title: Altered "set-point" of the hypothalamus determines effects of cortisol on food intake, adiposity, and metabolic substrates in sheep.
abstract: Chronic elevation of glucocorticoid concentrations is detrimental to health. We investigated effects of chronic increase in plasma cortisol concentrations on energy balance and endocrine function in sheep. Because food intake and reproduction are regulated by photoperiod, we performed experiments in January (JAN) and August (AUG), when appetite drive is either high or low, respectively. Ovariectomized ewes were treated (intramuscularly) daily with 0.5mg Synacthen Depot(R) (synthetic adrenocorticotropin: ACTH) or saline for 4 wk. Blood samples were taken to measure plasma concentrations of cortisol, luteinising hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), leptin, insulin, and glucose. Adrenocorticotropin treatment increased concentrations of cortisol. During JAN, treatment reduced food intake transiently, but increased food intake in AUG. Leptin concentrations were reduced and glucose concentrations were greater in AUG, and insulin concentrations were similar throughout the year. Treatment with ACTH increased leptin concentrations in AUG only, whereas insulin concentrations increased in JAN only. Synacthen treatment increased glucose concentrations, with a greater effect in JAN. Changes in truncal adiposity and ACTH-induced cortisol secretion were positively correlated in JAN and negatively correlated in AUG. Treatment reduced the plasma LH pulse frequency in JAN and AUG, with an effect on pulse amplitude in JAN only. Treatment did not affect plasma GH or FSH concentrations. We conclude that chronically elevated cortisol concentrations can affect food intake, adiposity, and reproductive function. In sheep, effects of chronically elevated cortisol concentrations on energy balance and metabolism depend upon metabolic setpoint, determined by circannual rhythms.
authors.affiliation: Department of Physiology, Building 13 F, Wellington Road, Monash University, VIC 3800, Australia. belinda.henry@med.monash.edu.au
authors.forename: B A
authors.initials: BA
authors.lastname: Henry
authors.forename: D
authors.initials: D
authors.lastname: Blache
authors.forename: F R
authors.initials: FR
authors.lastname: Dunshea
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000502:physiology; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D012621:Seasons; D012756:Sheep / Q000378:metabolism / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D006854:Hydrocortisone