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Evaluating the involvement of glucocorticoid feedback on the reproductive effects of environmental chemicals
Citation:
FRAITES, M. P. AND R. L. Cooper. Evaluating the involvement of glucocorticoid feedback on the reproductive effects of environmental chemicals. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This purpose of this work is to determine which environmental chemicals activate the hypothalamic-pituitary-adrenal axis and to develop strategies to investigate if the activation of this axis serves as a mode of action by which these compounds alter reproductive function.
Description:
Acute and chronic stressors activate the hypothalamic-pituitary-adrenal (lIPA) axis and are known to suppress reproductive function through central negative feedback of the gonadal axis by glucocorticoids. Recently, several environmental chemicals known to attenuate or suppress the luteinizing hormone (LH) surge necessary for ovulation have also been shown to activate the lIPA axis. We hypothesize that the attenuation of the LH surge by some of these lIPA axis-activating compounds results from the central negative feedback effects of glucocorticoids. To test this hypothesis, the current study exposed female, regularly cycling, Long-Evans Hooded rats to a single oral dose of 150 mg/kg metam sodium (MS) or 0.1% methyl cellulose vehicle during the proestrous critical period (1100-1300 hours). This dose of MS stimulates a dramatic increase in adrenocorticotropin and corticosterone (CORT) within fifteen {Ilinutes of oral exposure and blocks the LH surge in proestrous rats. Acute CORT produ~t~S was inhibited by subcutaneous injection ofthe 11J3-hydroxylase inhibitor Metyrap~ne (MET) 40 minutes prior to oral exposure but unaffected by polyethylene (PEG) vehicle. Serum concentrations of LH during the surge (1800 hours) were suppressed in both PEGIMSand METIMS-treated rats compared to methyl cellulose-treated rats. These results indicate that suppression of MS-induced CORT secretion by MET does not rescue the LH surge. We conclude that glucocorticoid feedback following MS exposure is not the mode of action by which this compound suppresses the LH surge. Future studies will use this experimental design to determine the role ofcorticosteroid feedback on the reproductive effects of other environmental chemicals. This abstract does not necessarily reflect EPA policy.