Elevation of hypophysial portal concentrations of adrenocorticotropin secretagogues after fornix transection.

Glucocorticoid feedback inhibition at the level of the brain is extremely complex, involving feedback at both hypothalamic and suprahypothalamic levels. The hippocampus has been implicated as a suprahypothalamic mediator of such feedback, based on numerous lesion, stimulation, and steroid implantation studies. These reports, however, predated the isolation and characterization of CRF and recognition of the multifactorial control of ACTH release. Thus, it is not clear which hypothalamic ACTH secretagogues are under inhibitory control of the hippocampus. To answer this, we measured hypophysialportal concentrations of CRF, arginine vasopressin, and oxytocin in rats with fornix transections, which disrupt hippocampal communication with the hypothalamus. Hypophysial-portal blood was collected in rats exposed to either low or high circulating corticosterone concentrations in the presence or absence of the coincident stressor of hypotension. We observed that fornix transection produced hypersecretion of all three secretagogues. However, the pattern of hypersecretion differed for each as follows: 1) fornix transection did not affect either initial CRF secretion or the magnitude of the stress response, but made rats resistant to a high feedback signal during stress; 2) fornix transection led to initial arginine vasopressin hypersecretion, which remained sensitive to a high feedback signal; and 3) fornix transection led to initial oxytocin hypersecretion as well as resistance to a high corticosterone feedback signal during hypotension.