SEX-DIFFERENCES IN HYPOTHALAMIC-PITUITARY-ADRENAL RESPONDING TO ENDOTOXIN CHALLENGE IN THE NEONATE - REVERSAL BY GONADECTOMY

Exposure to endotoxin is known to activate hypothalamic-pituitary-adre nal (HPA) responses in both adult and neonatal animals. We have previo usly reported that female rat pups exhibit greater HPA responses to en dotoxin challenge than males. It is unclear, however, whether observed gender differences at this early age are mediated by gonadal factors. In the present investigation we assessed the effects of neonatal gona dectomy on HPA responses to endotoxin challenge in the developing rat. On the first day of life Long-Evans rat pups were gonadectomized or s ubjected to sham surgery. On the third day of life the pups were injec ted i.p. with 0.05 mg/kg Salmonella enteritidis endotoxin. Four hours following injection, trunk blood and tissues were collected for determ ination of plasma hormones and median eminence corticotropin-releasing hormone (CRH) content. Intact female rat pups were found to exhibit g reater plasma adrenocorticotrophic hormone (ACTH) and corticosterone r esponses to endotoxin challenge compared with male animals. Plasma cor ticosterone levels, both total and free steroid, were markedly altered by removal of gonads such that responding to endotoxin was elevated i n males, while it was reduced in females. In contrast, ACTH responding in male pups was not altered following gonadectomy, whereas female AC TH responses were significantly reduced compared with endotoxin-treate d intact controls. CRH levels in the median eminence were reduced foll owing endotoxin challenge to an equivalent extent in both male and fem ale pups and this effect was partially attenuated by the removal of go nadal hormones. These data suggest that sex differences in HPA respons es to immune challenge may be mediated at different levels of the HPA axis. Changes in HPA responses following gonadectomy may compensate fo r removal of gonadal steroid immunoregulatory influences in the neonat e.