INTENSIVE VENOUS SAMPLING OF ADRENOCORTICOTROPIC HORMONE IN RATS WITHSHAM OR PARAVENTRICULAR NUCLEUS LESIONS

Adrenocorticotropic hormone (ACTH) secretion from the anterior pituita ry is predominantly regulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) synthesized in neurons of the paravent ricular nucleus (PVN) of the hypothalamus. Secretion of ACTH occurs in pulsatile bursts. To explore the relationship between hypothalamic co ntrol and the pulsatile pattern of ACTH secretion, we measured ACTH in 2 min blood samples over 4 h in rats with intact and lesioned PVN dur ing hypovolemic-stress or control conditions and also measured median eminence (ME) levels of CRH, AVP, and oxytocin (OT). Mean plasma ACTH was highest in the sham lesioned-hypovolemic group, lowest in the sham lesioned-control soup and intermediate in the two PVN-lesioned groups . CRH in the ME was negligible in the lesioned animals and correlated with OT and AW. Pulsatile secretion was observed despite PVN ablation. Visual inspection of composite time series suggested different tempor al patterns of ACTH secretion. Principal components analysis of the in dividual ACTH time series revealed three significant eigenvectors whic h correlated differentially with the three treatment groups. Neither l esioned group had the steep rise over 10 min seen in plasma ACTH in th e non-lesioned groups. Delayed ACTH rise after 30-60 min occurred in a ll but the sham control group. Our data suggest that CRH is responsibl e for immediate secretion of ACTH in response to hypovolemic stress an d that regulators from non-PVN sites may be responsible for more delay ed secretion of ACTH in this setting. The persistence of ME AVP and OT levels in the face of >90% reduction in ME CRH levels leaves open the question of a role for one or both of these peptides in the delayed A CTH response following stress onset and in the generation of pulsatile ACTH secretory bursts.