Endocrine responses of ovariectomized ewes to i.c.v. infusion of urocortin

Urocortin is a novel corticotropin-releasing factor-like peptide, first isolated from the rat midbrain, which has anorexigenic properties, possibly associated with its involvement in the stress axis. Urocortin has been implicated in blood pressure regulation, ACTH release and feed intake, but its role as an integral component of the reproduction-nutrition axis has not been examined. The present experiment was designed to determine the effects of i.c.v. infusion of urocortin on feed intake and endocrine profiles of LH, GH, IGF-I, cortisol and leptin in ovariectomized ewes. Ewes were fitted with two laterocerebroventricular cannulae and urocortin was continuously infused in a linearly increasing manner from 0.001 microg/h on day 0, to a maximum of 31.6 microg/h on day 5. Blood samples were collected via jugular catheters at 10 min intervals for 4 h on day 1, 3 and 5, and assayed by RIA for LH, GH, IGF-I, cortisol and leptin. All ewes were allowed free access to feed and water, and feed intake was recorded daily. Urocortin-infused ewes responded with a significant decrease in feed intake beginning on day 1 (P<0.02) and were aphagic for the remainder of the experiment. Serum concentrations of LH were elevated in individual samples from urocortin-treated compared with saline-treated ewes on day 3 (treatment x day x sample, P=0.05), but were not different on day 1 or 5. Mean serum concentrations of GH increased (P<0.04) over days with urocortin treatment, although concentrations of IGF-I were not influenced by treatment (P>0.5). Serum concentrations of cortisol were markedly increased by urocortin treatment (P<0.001). Leptin tended to be influenced by treatment and day (P=0.08), with leptin levels tending to be elevated in urocortin-treated vs saline-treated ewes on day 5 (P=0.08). The ability of urocortin to decrease feed intake while increasing LH, GH, cortisol and leptin provides evidence that urocortin is not only an integral component of the stress axis, but possibly of the nutrition-reproduction axis in sheep.