The Effects of Corticotropin-Releasing Factor on Adrenocorticotropin Secretion from Perifused Pituitariesin vitro: Rapid Inhibition by Glucocorticoids*

Abstract

The effect of synthetic corticotropin-releasing factor (CRF) and glucocorticoids on ACTH secretion from rat anterior pituitaries was examined in vitro. Pituitaries were cut into 12 fragments and perifused at 37.degree. C with a modified Krebs buffer. CRF produced a rapid (1-min), Ca2+-dependent rise in ACTH secretion, with a half-maximally effective concentration of about 1 nM. ACTH secretion declined after 90 min of continuous perfusion with CRF. In vivo, glucocorticoids can inhibit stress-induced ACTH secretion with a latency of a few seconds. Coperifusion with 10-7 M cortisol, corticosterone or dexamethasone, but not cortisone, inhibited the effect of CRF by nearly 50%. The latency of the inhibition was between 10 and 20 min, and the inhibition persisted for as long as the steroid was present. Basal secretion was unaffected by steroid treatment for 30 min. These results indicate that rapid inhibition of stimulated ACTH secretion can occur at the level of the pituitary in vitro, but that the feedback differs from that observed in vivo in terms of the longer latency and the persistence of the response.