Lipopolysaccharide modulation of eicosanoid and corticotrophin-releasing hormone release from rat hypothalamic explants and astrocyte cultures in vitro: Evidence for the involvement of prostaglandin E2 but not prostaglandin F(2α) and lack of effect of nerve growth factor

Bacterial lipopolysaccharide (LPS) and prostaglandins (PG) E₂ and F(2α) are putative activators of the hypothalamo-pituitary-adrenal axis. Certain of the biological effects of LPS may be mediated by cytokines such as interleukin-1β (IL-1β), while IL-1β itself may operate via induction of the prostaglandins and/or nerve growth factor (NGF). As IL-1β stimulates the release of corticotrophin-releasing hormone (CRH) from acute rat hypothalamic explants directly, the effects of these substances on the release of CRH in vitro were investigated in short- and medium-term (20 and 60 min) incubations. The effect of LPS on the release of PGE₂ and PGF(2α) from these explants, as well as from cortical astrocyte cultures, was also studied. LPS did not modify the release of CRH, PGE₂ or PGF(2α) in 20-min incubations. In 60-min incubations, LPS stimulated the release of PGE₂, whereas the release of CRH was weakly, but significantly, reduced; PGF(2α) was not altered. PGE₂ significantly stimulated CRH release in the 60-min but not in the 20-min experiments. This effect appeared to be selective for PGE₂, since PGF(2α) did not modify CRH release, alone or in combination. LPS also selectively released PGE₂ but not PGF(2α) from cortical astrocyte cultures after 24-h incubation. NGF had no effect on the release of explant CRH, regardless of the length of incubation. It was concluded that neither LPS nor NGF acutely stimulate the hypothalamo-pituitary-adrenal axis by a direct action on hypothalamic CRH, while hypothalamic PGE₂ may mediate, at least in part, certain of the neuroendocrine responses to LPS.