title: Interleukin-1 potentiates basal and AVP-stimulated ACTH secretion in vitro--the role of CRH pre-incubation.
abstract: The acute-phase cytokine interleukin-1 (IL-1) is known to activate the hypothalamic pituitary adrenal axis, primarily via corticotropin releasing hormone (CRH). The aim of this study was to determine whether IL-1beta could directly stimulate ACTH secretion from perifused equine anterior pituitary cells, and whether CRH pre-incubation affected corticotroph responsiveness. Isolated equine anterior pituitary cells were pre-incubated with media containing 10 nM CRH or vehicle for 20 hours before being loaded onto columns and perifused with 0.02 nM CRH and 100 nM cortisol. Columns were given a 5-minute pulse of arginine vasopressin (AVP, 10 nM), perifused for 4 hours with 0 (control) or 1 nM IL-1beta, then given a further 5-minute pulse of AVP (10nM). ACTH was measured in 5 minute fractions. In the setting of CRH pre-incubation, cells perifused with IL-1beta for 4 hours showed increased basal ACTH secretion compared to control (114 +/- 6 pM vs. 86 +/- 4 pM [means +/- S.E.M.], p < 0.001) and a significantly greater ACTH response to the final AVP pulse (240 +/- 32% vs. 96 +/- 30%, p = 0.009, expressed as % of ACTH response to the initial AVP pulse). The potentiation of AVP-stimulated ACTH release by IL-1 was not observed in cells pre-incubated with vehicle alone. In conclusion, IL-1 increases ACTH release in equine corticotroph cells pre-incubated with CRH and potentiates responsivity to AVP.
authors.affiliation: Department of Endocrinology, Christchurch Hospital, New Zealand.
authors.lastname: Prickett TCR
authors.forename: W J
authors.initials: WJ
authors.lastname: Inder
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: R A
authors.initials: RA
authors.lastname: Donald
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone