Ali Hassan

D.R. Mason & A.M.A. Hassan

Department of Zoology, University of Canterbury, Christchurch, New Zealand.

Corticotropin-releasing hormone (CRH) stimulates adrenocorticotropin (ACTH) release from pituitary corticotropes via a cyclic AMP-dependent mechanism. The ACTH response is reduced following prolonged or repeated CRH stimulation. This study was aimed at investigating the role of adenylate cyclase in mediating this desensitization.

Column-perifused ovine anterior pituitary cells were pre-treated for 3 h with 10 μM forskolin or 0.1 nM CRH prior to re-stimulation with 10 nM CRH. The magnitude of the ACTH response to re-stimulation was compared with the response of control cells which were treated with 10 nM CRH alone. Pre-treatment with both forskolin and CRH significantly (p<0.05) reduced subsequent CRH-stimulated ACTH release (by 36.2 ± 5.7% [n=10] and 59.5 ± 5.2% [n=6] respectively). This reduction did not appear to be due a depletion of intracellular ACTH stores since both pre-treatments decreased the percentage of intracellular ACTH released upon re-stimulation. In addition, pre-treatment of cells with forskolin did not result in a reduction in the ACTH response to subsequent stimulation with 50 mM KCl.

We conclude that activation of adenylate cyclase can mediate desensitization of the ACTH response to CRH, most likely through cyclic AMP-dependent phosphorylation of a component of the intracellular signalling pathway.

Presented at FEBS Special Meeting on Cell Signalling Mechanisms, Abstract P2-037, 1997.