A STRESS-SENSITIVE CHEMOKINERGIC NEURONAL PATHWAY IN THE HYPOTHALAMOPITUITARY SYSTEM

Recently we found that cytokine-induced neutrophil chemoattractant inf luenced anterior pituitary hormone release in vitro. These observation s prompted us to investigate the possibility of the existence of cytok ine-induced neutrophil chemoattractant in the hypothalamus. Immunohist ochemistry showed that cytokine-induced neutrophil chemoattractant-lik e immunoreactivity existed in the paraventricular hypothalamic nucleus , the supraoptic nucleus. both the internal and the external layers of the median eminence and the posterior pituitary. Since the paraventri cular hypothalamic nucleus plays a pivotal role in response to stressf ul stimuli, we examined the effect of a single episode of immobilizati on stress on cytokine-induced neutrophil chemoattractant messenger RNA expression in the paraventricular hypothalamic nucleus. Immobilizatio n stress induced strong hybridization signals of cytokine-induced neut rophil chemoattractant messenger RNA in the parvocellular and magnocel lular subdivision of the paraventricular hypothalamic nucleus within 1 5 min, and cytokine-induced neutrophil chemoattractant-like immunostai ning intensity in the posterior pituitary started to increase around t he periphery of the posterior lobe at 30 min after stress and extended to the whole lobe at 1 h after stress. The increase in the serum cyto kine-induced neutrophil chemoattractant in response to stress showed a kinetically biphasic pattern. A first phase occurred within 15 min wh ich may be due to an immediate release of stored cytokine-induced neut rophil chemoattractant in the neurohypophysis, since hypophysectomy co mpletely blocked this phase. A second phase may reflect the release of newly synthesized cytokine-induced neutrophil chemoattractant in the paraventricular hypothalamic nucleus and/or peripheral cytokine-induce d neutrophil chemoattractant, since hypophysectomy could not reduce th is phase. These data suggest that cytokine-induced neutrophil chemoatt ractant in the paraventricular hypothalamic nucleus was immediately sy nthesized in response to stress, and then released into the peripheral blood via the hypothalamo-neurohypophysial system, revealing the pres ence of a stress-sensitive chemokinergic neuronal pathway in the hypot halamo-pituitary system. Copyright (C) 1996 IBRO.