Ali Hassan

Ali 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, 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 CRH and forskolin 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 to a depletion of intracellular ACTH stores since both pre-treatments decreased the percentage of intracellular ACTH released upon re-stimulation. In addition, pretreatment with of cells with forskolin did not result in a reduction in the ACTH response to subsequent stimulation with 50 mM KCl. Pre-treatment with the cyclic AMP analogue 8-bromo-cAMP at concentrations of 1.25 and 2.5 mM did not reduce the ACTH response of the cells. Pre-treatment with 0.1 nM CRH for 3 h followed by re-stimulation with 10 μM forskolin for 1 h resulted in an 84 ± 3.6% [n=3] reduction in ACTH response compared with cells treated with 10 μM forskolin alone.

I 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, possibly adenylate cyclase.

New Zealand Medical Journal 110:399, 1997.

Presented at the Canterbury Medical Research Society Scientific Meeting, Christchurch, New Zealand, 1997.