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 contro l of ACTH secretion, we used an in vitro perifusion model with dispersed eq uine anterior pituitary cells. To approximate the in vivo milieu in the hor se, 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 inc reased as both the CRH (p<0.001) and the AVP (p<0.001) concentration increa sed 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 rele ase at 0 pmol CRH/L (p=0.008), having no effect at 2 pmol CRH/L and potenti ating it at 20 pmol CRH/L (p=0.026). We conclude that (1) CRH at high physi ological levels has a "permissive" role in preventing the cortisol inhibiti on of the ACTH response to AVP, and (2) basal cortisol levels have a "permi ssive" action in priming the HPA axis for maximal responsiveness to stimula ted levels of CRH and AVP.