Peptide histidine isoleucine-induced elevations in ACTH and corticosterone in the rat

Peptide histidine isoleucine (PHI) is one of many neuropeptides found in both the periphery and the central nervous system (CNS). In the present work, we compared the effects of intravenous (IV) and hypothalamic (PVN) administration of PHI on plasma ACTH and corticosterone (CORT) secretion 2 h after the onset of light in fasted, freely moving male rats. The PVN administration of PHI (0.15, 0.30, 1.50, and 3.0 nmol/rat) elicited significant, dose-dependent increases in plasma ACTH and CORT concentrations that were maximal at 15 min postadministration and fell gradually over 60-120 min. The highest dose of PHI increased ACTH and CORT to 821% and 340% of time-matched control levels, respectively. The IV injection of PHI (3.0 nmol/rat) also raised plasma ACTH and CORT levels in these animals. However, the peak response (at 15 min postinjection) to the same dose of PHI was much lower following IV administration (ACTH 188% of control; CORT 210% of control) than after PVN administration. These results suggest that endogenous PHI may be a physiological regulator of ACTH and CORT secretion in rats and that the PVN is a major site for its action.