Characteristics of the ACTH response to repeated pulses of corticotrophin-releasing factor and arginine vasopressin in vitro

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Abstract
A multi-column perifusion system was used to investigate the dynamics of the dose–response relationships of ACTH release by ovine pituitary cells when stimulated by both corticotrophin-releasing hormone (CRF) and arginine vasopressin (AVP) given alone and in combination. A dose–response relationship was obtained when 10-min pulses were given at 60-min intervals over the range of 0·002–2000 nmol CRF/l and 1–2000 nmol AVP/l, with a minimum effective concentration of 0·02 nmol CRF/l or 1 nmol AVP/l. When AVP was given together with CRF, the expected potentiation of the ACTH response occurred when compared with the summed response of these secretagogues given separately. At the higher concentrations of CRF and AVP used, the ACTH responses to repeated pulses decreased with time during the experiment. The rate of this loss of responsiveness was significantly correlated to the size of the response to the first pulse (for CRF: r = 0·89, Pr = 0·95, P < 0·01), being greatest when the response was potentiated by adding the secretagogues together (for CRF plus AVP: r = 0·95, P P < 0·001) less after AVP plus CRF than after CRF alone. Also the rapidity with which ACTH concentrations fell after removal of the stimulus from the perifusion medium was significantly (P P in vitro and potentiated the initial response to CRF rather than prolonging its action. Desensitization to each stimulant appeared to act by a mechanism independent of the other and therefore appeared to occur at or near the receptor level and be unrelated to the availability of ACTH. J. Endocr. (1988) 117, 387–395