Ali Hassan

D.R. Mason, A.M.A. Hassan & S.R.R. Chacko

Department of Zoology, University of Canterbury, New Zealand.

CRH and VP are key regulators of adrenocorticotropin (ACTH) secretion from the anterior pituitary. Following repeated or prolonged exposure to either CRH or VP, ACTH responsiveness is reduced. Our aim was to compare the characteristics of desensitisation to CRH and VP in perifused ovine anterior pituitary cells.

Pre-treatment of cells with VP reduced the response to a subsequent 5 min, 100 nM VP pulse. VP pre-treatment for 25 min at various concentrations showed that desensitisation was dose-dependent, with 2 nM being the lowest effective concentration. Significant desensitisation was observed following pre-treatment with 5 nM VP for as briefly as 5 min. Desensitisation was greater following a 10 min pre-treatment but longer exposures caused no further reduction in response. Pre-treatment with 0.1 nM CRH for either 25 or 50 min did not cause any reduction in response to a subsequent 5 min, 10 nM CRH pulse. However, when the pre-treatment concentration was increased to 1 nM significant desensitisation was observed, with a greater reduction in response being observed after 50 min pre-treatment. Resensitisation was investigated by pre-treating cells with either 10 nM VP for 15 min or 1 nM CRH for 50 min, followed by a variable ‘recovery period’ during which cells were perifused with medium alone before the VP or CRH pulse. Recovery was progressive and was complete after 40 min for VP and 100 min for CRH.

In summary, desensitisation to VP occurred rapidly, at low concentrations, and was readily reversible. It occurred at concentrations and durations of VP treatment within the endogenous range, suggesting that desensitisation may play a key role in regulating ACTH secretion in vivo. Cells appear less susceptible to CRH desensitisation, and therefore its role is less clear. However, if, as has been suggested, CRH acts to set corticotroph gain while VP is the main dynamic regulator, any change in responsiveness to CRH may influence the overall control of ACTH secretion.

International Congress of Neuroendocrinology, Bristol, U.K. 2002.