Ali Hassan

Ali M.A. Hassan & Drusilla R. Mason

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

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, or desensitised. The aim of this study was to investigate the time- and dose-dependency of this desensitisation to AVP, and the rate of recovery from desensitisation in ovine anterior pituitary cells.

Perifused cells were stimulated with 5 min pulses of 100 nM AVP after 100, 180 and 260 min of perifusion, resulting in three similar ‘peaks’ of ACTH secretion. Pre-treatment with AVP prior to the second pulse caused a reduction in response, or desensitisation. The extent of this desensitisation was determined by expressing the response to the second pulse as a percentage of the mean of the responses to the first and third pulses. When the concentration of the AVP pre treatment was varied between 0.1 and 50 nM AVP, while the duration was held constant at 25 min, there was a significant reduction in response after pre-treatment with AVP concentrations as low as 2.0 nM (n=3, p<0.001). This reduction increased with increasing pre-treatment dose until the second AVP pulse caused no additional increase in ACTH release following pre-treatment with 50 nM AVP. The IC₅₀ of this AVP dose-dependency was calculated to be 6.54 nM. When the duration of the pre treatment was varied between 0 and 25 min, while the AVP concentration was held constant at 5 nM, there was a reduction in response of 39.4 ?? 8.6% (n=3, p<0.05) following pre treatment of only 10 min. Longer pre treatment did not elicit any further reduction in response. To investigate recovery from desensitisation, cells were stimulated with a single 100 nM AVP pulse, which was preceded by a pre-treatment with 10 nM AVP for 15 min and followed by a variable ‘recovery period’ during which the cells were perifused with medium alone. When the 100 nM AVP pulse was applied immediately upon termination of the pre treatment (ie 0 min recovery) the magnitude of the response to the pulse was 63.3 ?? 5.4% (n=7, p<0.0001) less than the response seen in controls that were not pre treated. With a 10 min recovery period between the pre treatment and the test pulse there was a partial recovery in response. The extent of recovery increased with increasing recovery time and was complete at 40 min.

These data show that desensitisation of the ACTH response to AVP occurs rapidly, at low AVP concentrations, and is readily reversible. Furthermore the AVP concentrations and durations at which desensitisation occurs are within the endogenous range, suggesting that desensitisation may play a role in the regulation of ACTH secretion in vivo.

Proceedings of the Endocrine Society of Australia 42:242, 1999.

Presented at the New Zealand Society of Endocrinology Scientific Meeting, Mt Maunganui, New Zealand, 1999.