Ali Hassan

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

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

Recently we have shown that treatment of ovine anterior pituitary cells with arginine vasopressin (AVP), an important regulator of ACTH secretion, results in desensitization to a subsequent stimulation with AVP. This desensitization was found to be rapid and occurred at low AVP concentrations (e.g. pre-treatment with 5 nM AVP for 5 min caused significant desensitization). Since CRH is also an important regulator of ACTH secretion, the aims of this study were: firstly to determine whether the ACTH response to CRH is similarly sensitive to desensitization following prior CRH exposure, and secondly to investigate the effect of CRH on AVP-induced desensitization. When perifused anterior pituitary cells were treated with a 5 min pulse of CRH (10 nM) at 200 min, the magnitude of the response to the pulse was not significantly reduced following pre-treatment with 0.1 nM CRH for either 25 or 50 min immediately prior to the pulse. If the CRH pre-treatment concentration was increased to 1 nM, the response to the pulse was reduced by 36.4 ± 11.6% (n=6, p<0.05) after a 25 min pre-treatment and by 52.2 ± 13.0% (n=6, p<0.01) after a 50 min pre-treatment. To investigate the effect of CRH on AVP-induced desensitization, perifused cells were treated with 5 min, 100 nM AVP pulses after 120, 200 and 280 min, and were continuously exposed to a low level (0.01 nM) of CRH from 80 min onward. A 15 min, 5 nM AVP pre-treatment immediately preceded the second pulse. The extent of the desensitization was assessed by expressing the response to the second pulse as a percentage of the mean of the responses to the first and third pulses, which acted as controls. AVP pre-treatment reduced the response to the second AVP pulse more in the presence of CRH than in its absence (i.e. by 37.3 ± 1.9% cf. 26.8 ± 1.7%, n=7, p<0.05). These data suggest that the ACTH response of ovine anterior pituitary cells is less sensitive to desensitization with CRH than AVP, and that CRH does not ‘protect’ these cells from AVP-induced desensitization.

Presented at the 11th International Congress of Endocrinology, Sydney, Australia, Abstract P1407, 2000.