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 F2α and lack of effect of nerve growth factor

Abstract

Bacterial lipopolysaccharide (LPS) and prostaglandins (PG) E2 and F2 alpha are putative activators of the hypothalamo-pituitary-adrenal axis. Certain of the biological effects of LPS may be mediated by cytokines such as interleukin-1 beta (IL-1 beta), while IL-1 beta itself may operate via induction of the prostaglandins and/or nerve growth factor (NGF). As IL-1 beta 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 PGF2 alpha from these explants, as well as from cortical astrocyte cultures, was also studied. LPS did not modify the release of CRH, PGE2 or PGF2 alpha in 20-min incubations. In 60-min incubations, LPS stimulated the release of PGE2, whereas the release of CRH was weakly, but significantly, reduced; PGF2 alpha 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 PGF2 alpha did not modify CRH release, alone or in combination. LPS also selectively released PGE2 but not PGF2 alpha from cortical astrocyte cultures after 24-h incubation. NGF had no effect on the release of explant CRH, regardless of the length of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)