Interleukin-1 Potentiates Basal and AVP-Stimulated ACTH Secretion In Vitro - The Role of CRH Pre-Incubation

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-1β 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-1β, then given a further 5-minute pulse of AVP (10 nM). ACTH was measured in 5 minute fractions. In the setting of CRH pre-incubation, cells perifused with IL-1β 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.

Key words

Equine Pituitary - Perifusion - Cortisol - Leukemia Inhibitory Factor