Interactions of CRH, AVP and cortisol in the secretion of ACTH from perifused equine anterior pituitary cells: "permissive" roles for cortisol and CRH.

To further elucidate the interaction of CRH, AVP and cortisol in the control of ACTH secretion, we used an in vitro perifusion model with dispersed equine anterior pituitary cells. To approximate the in vivo milieu in the horse, CRH was perifused continuously (at 0, 2 and 20 pmol/L) and 5-min pulses of AVP (0, 1, 3 and 10 nmol/L) were given every 30 min in the presence of 0 or 100 nmol/L cortisol. Total (baseline + incremental) ACTH secretion increased as both the CRH (p<0.001) and the AVP (p<0.001) concentration increased and interaction between CRH and AVP was significant (p=0.042). Cortisol reduced total ACTH secretion in the presence of 2 pmol CRH/L (p=0.001) but not 0 or 20 pmol CRH/L. For incremental ACTH there was interaction between CRH and AVP (p<0.0001), with increased secretion at higher concentrations, and no significant main effect of cortisol. There was significant (p=0.001) interaction between cortisol and CRH, with cortisol attenuating ACTH release at 0 pmol CRH/L (p=0.008), having no effect at 2 pmol CRH/L and potentiating it at 20 pmol CRH/L (p=0.026). We conclude that (1) CRH at high physiological levels has a "permissive" role in preventing the cortisol inhibition of the ACTH response to AVP, and (2) basal cortisol levels have a "permissive" action in priming the HPA axis for maximal responsiveness to stimulated levels of CRH and AVP.