HYPOTHALAMIC INVOLVEMENT IN THE ACTIVATION OF THE PITUITARY-ADRENOCORTICAL AXIS BY NERVE GROWTH-FACTOR

Intravenous injection of nerve growth factor (NGF) into rats produces a dose-dependent (from 0.1 to 5 nmol/kg) increase in circulating conce ntrations of adrenocoticotropin (ACTH) and corticosterone. We have inv estigated whether this effect is produced through a direct action on a component of the hypothalamo-pituitary-adrenocortical axis. NGF (50 a nd 500 nM), added to the incubation medium of in vitro isolated pituit ary segments or dispersed adrenal cells, did not modify either basal a nd stimulated release of biologically active or immunoreactive ACTH or release of corticosterone, respectively. The presence of NGF in the i ncubation medium of in vitro isolated hypothalami produced a dose-depe ndent (from 150 to 600 nM) increase of both release and content of som e material with corticotropin-releasing, bioactivity. The nature of th is corticotropin-releasing bioactivity was determined directly by radi oimmunoassays. Results have indicated that NGF induced an increase of both release and content of hypothalamic arginine-vasopressin (AVP), w hile no changes were observed in the release and content of hypothalam ic corticotropin-releasing hormone (CRH). These results suggest that a drenocortical stimulation by NGF in vivo could be mediated by the rele ase of hypothalamic AVP rather than CRH. The finding that in vivo NGF stimulatory effect was not abolished by the specific CRH antagonist al pha-helical CRH(9-41), while it was accompanied by an increase in circ ulating AVP levels, supports this interpretation. However, the fact th at the hypothalamus is stimulated in vitro by NGF concentrations highe r than those expected to reach this structure after systemic injection of active doses raises the possibility that other brain areas such as the hippocampus participate in NGF-induced adrenocortical activation.