Involvement of central, but not placental corticotropin releasing hormone (CRH) in heat stress induced immunosuppression during pregnancy

To clarify whether corticotropin releasing hormone (CRH) and beta -endorphin (beta EP) system mediate maternal immunosuppression in pregnant rats exposed to heat through central or placental pathway, we examined the effects of intravenous (iv) (100 or 500 mug) or intracerebroventricular (icv) (5 mug) administration of CRH receptor antagonist alpha -helical CRH (9-41) on splenic natural killer cell activity (NKCA) as well as beta EP in blood, pituitary lobes, and placenta in pregnant rats at 15 to 16 days gestation. Two-way ANOVA revealed that heat reduced NXCA and elevated blood and pituitary beta EP but did not change placental beta EP. Iv administered 500 mug and icv administered alpha -helical CRH reversed the reduced NKCA and the elevated pituitary beta EP, while iv administration of 100 mug alpha -helical CRH did not. The increased blood beta EP was reversed by iv 100 and 500 mug alpha -helical CRH and icy administration. Both iv and icy administrations reduced placental beta EP independent of heat exposure. Thus, the response of placental beta EP to iv administration of alpha -helical CRH seemed to be stronger than that of pituitary beta EP. These results indicate that alpha -helical CRH which acts on pituitary beta EP antagonizes heat-induced immunosuppression during pregnancy, suggesting that immunosuppression produced by heat stress during pregnancy is mediated by the central CRH system. The placental CRH-beta EP system seems unlikely to be involved in the immunosuppression. Physiologic roles of placental CRH and opioid system should be clarified by future in vitro experiments using placenta specimen including placental immunocyte. (C) 2001 Academic Press.