title: The effect of the alpha-2-adrenergic agonist, clonidine, on secretion patterns and rates of adrenocorticotropic hormone and its secretagogues in the horse.
abstract: Alpha-2-adrenoceptor activation may lower adrenocorticotropic hormone (ACTH) by reducing secretagogue input and/or increasing the release of an inhibitory factor (CIF). To investigate this, we gave clonidine, an alpha-2-agonist, to seven horses, and collected pituitary venous blood every minute for 20 min before treatment and 40 min after treatment. Six horses were given saline vehicle. Mean secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and ACTH were calculated before and during four 5-min then two 10-min periods after clonidine or saline. Reduction in ACTH secretion without corresponding changes in CRH and/or AVP would imply the presence of CIF. Secretion rates of ACTH (P = 0.008) and AVP (P = 0.0005) fell after clonidine and remained lower than baseline values for 20 min and 10 min, respectively. The CRH secretion rate decreased slightly but not significantly after clonidine. In controls, hormone secretion rates did not alter during the experiment. Multiple linear regression showed that CRH and AVP secretion accounted for 69% (treated) or 45% (controls) of the variation in ACTH secretion (P < 0.0001 for each). CRH alone contributed 80% (treated) or 76% (controls) of the fit to this model, which is consistent with the concept that CRH 'sets the gain' of the response of corticotrophs to fluctuations in AVP. Accordingly, minute-to-minute changes in pituitary concentrations of AVP and ACTH were synchronous when all data were considered (% concordant changes: controls, 68%, P < 0.0001; treated, 76%, P < 0.0001) and the percentage of concordant movement was unaffected by clonidine (before 72%; after 73%; P = 0.80). In treated horses but not controls, the ratio between the secretion rates of ACTH and AVP fell (P = 0.009), while the ACTH : CRH ratio tended to fall after clonidine, implying reduced responsiveness to stimulation. Moreover, one horse showed a drop in ACTH and a rise in CRH and AVP secretion after clonidine. We conclude that in horses alpha-2-adrenoceptor activation lowers ACTH secretion primarily by reducing the secretion of AVP and possibly CRH. While there was some evidence that a CIF may participate in the clonidine-induced suppression of ACTH, the subtlety of the discordance between ACTH and its secretagogues in most horses and the rarity of complete dissociation indicate that it does not play a major role.
authors.affiliation: Department of Endocrinology, Christchurch Public Hospital, Christchurch, New Zealand. alexands@lincoln.ac.nz
authors.forename: S L
authors.initials: SL
authors.lastname: Alexander
authors.forename: C H
authors.initials: CH
authors.lastname: Irvine
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism; D006736:Horses / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000098:blood supply; D014680:Veins
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003000:Clonidine; D006854:Hydrocortisone