title: Evidence that the central noradrenergic and adrenergic pathways activate the hypothalamic-pituitary-adrenal axis in the sheep.
abstract: These studies were undertaken to test the hypothesis that stimulation of the central noradrenergic and adrenergic pathways activates the hypothalamic-pituitary-adrenal axis in vivo in the conscious sheep. Blood samples were taken at 10-min intervals over 4 h to establish the baseline state, and then each animal received an intracerebroventricular (icv) injection of NaCl (control animals) or catecholamine [norepinephrine (NE) or epinephrine (EPI)]. A more frequent rate of venous sampling was used for the 30-min period after the icv injection, after which time the 10-min rate of blood sampling was continued for another 3.5 h. NaCl (n = 4) caused no change in pituitary-adrenal secretion. In contrast, 10 micrograms NE (n = 4) caused acute 1.9- and 3.2-fold increases in mean plasma ACTH and cortisol levels over the 1 h period post injection, and 1.6- and 2.3-fold increments in their concentrations over the 4 h postinjection period. Although 10 micrograms EPI (n = 4) did not elevate mean plasma ACTH, it produced significant 1.7- and 1.5-fold increases in plasma cortisol during the 1- and 4-h periods post injection. However, when 100 micrograms EPI was injected (n = 4), acute 9.5- and 5.5-fold increases in plasma ACTH and cortisol were seen over the 1 h period post injection, and 6.1- and 4.2-fold increments in their plasma concentration were noted during the entire post-injection period. To determine the predominant site of action of the catecholamines, we also examined the ability of NE and EPI to release ACTH from cultured ovine anterior pituitary cells. NE and EPI (10(-9)-10(-6) M) stimulated the release of ACTH in a dose-dependent manner, but with maximal increments only 1.5-fold greater than the basal secretion. NE and EPI also increased the maximal ACTH response to CRF, but did not alter the maximal ACTH release induced by arginine vasopressin.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Prince Henry's Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: J P
authors.initials: JP
authors.lastname: Liu
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
authors.forename: D
authors.initials: D
authors.lastname: Engler
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007700:Kinetics; D009434:Neural Pathways / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D012756:Sheep / Q000502:physiology*
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine