Ali Hassan

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

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

The release of adrenocorticotropin (ACTH) from the pituitary gland is a key component in the vertebrate response to chronic stress. At least two hypothalamic hormones, including arginine vasopressin (AVP), are important in regulating ACTH release from the anterior pituitary. It has been found that following repeated or long-lasting stimulation of anterior pituitary cells with AVP their ACTH responsiveness is reduced is reduced or desensitized. The aim of this study was to determine the time- and dose-dependency of this desensitization to AVP in ovine anterior pituitary cells.

Perifused ovine anterior pituitary cells were stimulated with three 5 min pulses of 100 nM AVP at 80 min intervals. In experimental treatments the second pulse was preceded by a pre-treatment with AVP of varying concentration and duration. Desensitization was calculated as the reduction in response to the second pulse compared to the mean of the responses to the first and third pulses. In control columns there was no reduction in response to the second pulse.

After pre-treatment with 5 nM AVP for 10 min there was a reduction in ACTH secretion in response to 100 nM AVP of 37.7 ± 4.5% (p<0.05). Pre-treatment for longer than 10 min did not elicit any further reduction in response. When the pre-treatment duration was held constant at 25 min a dose-dependent reduction in response was observed. There was a significant reduction in response after pre-treatment with AVP concentrations as low as 2.0 nM (p<0.001) while there was no additional response to 100 nM AVP after pre treatment with 50 nM AVP. This reduction in response had an IC₅₀ of 6.0 nM. When the three 100 nM AVP pulses were replaced with 5 min pulses with 50 mM KCl (a non specific stimulus for ACTH release) there was no reduction in response after pre treatment with 5 nM AVP for 25 min. This suggests that the reduction in response was due to a true desensitization process rather than reflecting a general lack of responsiveness of the cells.
These data show that desensitization of the ACTH response to AVP can occur at pulse concentrations and durations which are within the endogenous range, raising the possibility that desensitization may play a role in the regulation of ACTH secretion in vivo.

New Zealand Medical Journal 112:280, 1998.

Presented at the Canterbury Medical Research Society Scientific Meeting, Christchurch, New Zealand, 1998