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 β-endorphin (βEP) 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 μg) or intracerebroventricular (icv) (5μg) administration of CRH receptor antagonist α-helical CRH (9-41) on splenic natural killer cell activity (NKCA) as well as βEP in blood, pituitary lobes, and placenta in pregnant rats at 15 to 16 days gestation. Two-way ANOVA revealed that heat reduced NKCA and elevated blood and pituitary βEP but did not change placental βEP. Iv administered 500 μg and icv administered α-helical CRH reversed the reduced NKCA and the elevated pituitary βEP, while iv administration of 100 μg α-helical CRH did not. The increased blood βEP was reversed by iv 100 and 500 μg α-helical CRH and icv administration. Both iv and icv administrations reduced placental βEP independent of heat exposure. Thus, the response of placental βEP to iv administration of α-helical CRH seemed to be stronger than that of pituitary βEP. These results indicate that α-helical CRH which acts on pituitary βEP 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-βEP 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.