Moderating influence of the drinking water disinfection by-product dibromoacetic acid on a dithiocarbamate-induced suppression of the luteinizing hormone surge in female rats.
The disinfection by-product dibromoacetic acid (DBA) has been found in female rats to increase circulating concentrations of both estradiol (E2) and estrone (E1). This effect is apparently due, at least in part, to a suppression in hepatic catabolism. The present study investigated whether DBA, by increasing sex steroid levels, is able either to augment the hypothalamic up-regulation involved in triggering a luteinizing hormone (LH) surge, or to affect the ability of the neurotoxicant sodium dimethyldithiocarbamate (DMDC) to block the surge. Sprague-Dawley rats were gavaged for 14 days with DBA (0-150mg/kg) and ovariectomized on dosing day 11, and at the same time implanted with an estradiol capsule to generate daily LH surges. An injection of 0.1mM/kg DMDC was administered at 13:00h on day 14 and blood was sampled over the afternoon. DBA induced a dose-related increase in total estrogens. For identified surges, areas under the LH curve partitioned into two groups, comprising the two lower (0 and 37.5mg/kg DBA) and the two higher (75 and 150mg/kg) treatment groups. Consequently, low and high DBA groups were compared and found to be significantly different. At 150mg DBA/0.1mM DMDC, the timing of an identifiable LH peak was comparable to non-DMDC females, unlike the 37.5mg DBA/0.1mM DMDC group in which the appearance of peak concentrations was delayed. A significant effect with DBA treatment alone was not present. Results indicated that this exposure to DBA induced a dose-related increase in total estrogen concentrations that paralleled a diminished DMDC blockade of the LH surge. The effect appeared to be attributable to an augmentation in the estrogen-associated up-regulation in brain mechanisms stimulating the surge.
Goldman
Jerome M
JM
Reproductive Toxicology Division, National Health & Environmental Effects Research Laboratory, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. goldman.jerome@epa.gov
Murr
Ashley S
AS
Buckalew
Angela R
AR
Ferrell
Janet M
JM
Cooper
Ralph L
RL
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D004125:Dimethyldithiocarbamate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood; D004970:Estrone / Q000097:blood; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood*; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010060:Ovulation / Q000097:blood / Q000187:drug effects*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D018508:Water Purification
D000085:Acetates; D004125:Dimethyldithiocarbamate; D004343:Drug Implants; D052244:Endocrine Disruptors; D004967:Estrogens; D014874:Water Pollutants, Chemical; D004970:Estrone; D004958:Estradiol; C088674:dibromoacetic acid; D007986:Luteinizing Hormone; D009638:Norepinephrine