Desensitization of the adrenocorticotropin responses to arginine vasopressin and corticotropin-releasing hormone in ovine anterior pituitary cells
Ali Hassan, Saramah Chacko & Drusilla Mason
Department of Zoology, University of Canterbury, Christchurch, New Zealand.
Following repeated or prolonged exposure to either corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP), pituitary adrenocorticotropin (ACTH) responsiveness is reduced. This study compared the characteristics of desensitization to CRH and AVP in perifused ovine anterior pituitary cells.
Desensitization to AVP occurred at relatively low AVP concentrations and was both rapid and readily reversible. Treatment for 25 min with AVP at concentrations greater than 2 nM caused significant reductions in the response to a subsequent 5 min 100 nM AVP pulse (IC50=6.54 nM). Significant desensitization was observed following pre-treatment with 5 nM AVP for as briefly as 5 min. Desensitization was greater following a 10 min pre-treatment, but longer exposures caused no further increase. Resensitization was complete within 40 min following 15 min treatment with 10 nM AVP. Continuous perifusion with 0.01 nM CRH had no effect on AVP-induced desensitization.
Treatment with 0.1 nM CRH for either 25 or 50 min caused no reduction in the response to a subsequent 5 min stimulation with 10 nM CRH. When the pre-treatment concentration was increased to 1 nM significant desensitization was observed, with a greater reduction in response occurring after 50 min treatment. Recovery of responsiveness was progressive following 50 min treatment with 1 nM CRH and was complete after 100 min.
Our data show that in the sheep AVP desensitization can occur at concentrations and durations of AVP exposure within the endogenous ranges. This suggests that desensitization may play a key role in regulating ACTH secretion in vivo. If, as has been suggested, CRH acts to set corticotroph gain while AVP is the main dynamic regulator, any change in responsiveness to CRH may significantly influence the overall control of ACTH secretion