Highly selective localization of leukotriene C 4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain

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While leukotriene C 4 (LTC 4) was originally identified as a potent bronchoconstrictor, the compound has versatile biological activities besides inflammatory reactions. Although the high content of LTC 4 has been reported in the hypothalamus and median eminence, the precise localization of the compound remained obscure. To elucidate its possible functions in the neuroendocrine systems, we determined immunohistochemical localization of LTC 4 synthase, a key enzyme to produce LTC 4 using mouse brains. Light microscopy and confocal laser scanning microscopy showed that LTC 4 synthase was selectively localized in the vasopressinergic magnocellular neurons of the hypothalamic paraventricular, supraoptic and suprachiasmatic nuclei and in the retrochiasmatic area, as well as in axons that emanated from these neurons to the pars nervosa of the pituitary gland. At subcellular level, however, LTC 4 synthase and arginine vasopressin appeared to localize differently within individual neurons. LTC 4 synthase immunoreactivity was also observed in the axons of the extrahypothalamic system including the bed nucleus of the stria terminalis, lateral habenular nucleus, midbrain central gray, medial amygdaloid nucleus and ventral septal area, although this immunoreactivity was relatively minor. The other brain regions did not contain LTC 4 synthase immunoreactivity. The distribution of LTC 4 synthase did not overlap with that of either oxytocin or luteinizing hormone releasing hormone. Therefore, LTC 4 is considered to be involved in neural functions of the brain magnocellular vasopressinergic system such as water retention. LTC 4 may also be involved in extrahypothalamic vasopressinergic neural functions including the regulation of learning and memory, social recognition memory, sexual and aggressive behavior, etc.