Acute and chronic estradiol replacements differentially alter corticosterone and COX-mediated responses to an inflammatory stimulus in female rats.

INTRODUCTION This study aimed to determine whether the previously reported differential effects of estradiol on inflammation-induced behavioral responses are in part explained through differential activation of the corticosterone-cyclooxygenase (CORT-COX) regulatory pathway. METHODS Prostaglandin E2 (PGE2), COX, and CORT levels were analyzed before and after a formalin administration (1% vs. 5%, representing different intensities of inflammatory stimuli). RESULTS In vehicle-treated rats, chronic estradiol administration increased corticosterone, and decreased COX and PGE2. After acute estradiol administration, although corticosterone serum levels were increased, COX protein levels were unchanged. In rats treated with formalin, PGE2 serum levels were higher in rats administered 5% formalin than vehicle- and 1%-treated rats. Significant correlations were observed between PGE2 serum levels, CORT serum levels, and COX protein levels. CONCLUSIONS Our results suggest that the administration of exogenous estradiol may mediate inflammatory responses by regulating the levels of PGE2 and/or CORT release, thereby mediating the nociceptive response to an inflammatory stimulus.