Science Inventory

DIBROMOACETIC ACID-INDUCED ELEVATIONS IN CIRCULATING ESTRADIOL: EFFECTS IN BOTH CYCLING AND OVARIECTOMIZED/STEROID-PRIMED FEMALE RATS

Citation:

Goldman, J M. AND A S. Murr. DIBROMOACETIC ACID-INDUCED ELEVATIONS IN CIRCULATING ESTRADIOL: EFFECTS IN BOTH CYCLING AND OVARIECTOMIZED/STEROID-PRIMED FEMALE RATS. REPRODUCTIVE TOXICOLOGY 17(5):585-592, (2003).

Description:

RTD-03-031
Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press).

Abstract

Oral exposures to high concentrations of the drinking water disinfection by-product dibromoacetic acid (DBA) over the course of 14 days have been found to disrupt estrous cyclicity in the female rat. In order to investigate possible alterations in the relevant hormonal regulatory mechanisms, female Sprague-Dawley rats were gavaged for 2 weeks with 270 mg/kg DBA, ovariectomized (OVX) and implanted with estradiol capsules. For these females, the induced luteinizing hormone (LH) surge in these animals showed a borderline suppression in peak LH concentrations that was accompanied by a marked increase in circulating estradiol. This elevation in estradiol was DBA dose-related and, for intact, normally cycling females receiving lower doses of DBA (60 and 120 mg/kg, 14 days), was present on the day of estrus, at a time when a dramatic fall from proestrous concentrations is normally evident. Evaluations of liver microsomal cytochrome P450 activity in OVX/estradiol-implanted rats showed a suppression in ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-deethylase (PROD) activity (indications of the activity of CYP1A and 2B, respectively- two key enzymes in estradiol oxidative metabolism). Phenobarbital (PhB) exposure in these animals did show induction of this activity, but was unable to lower E2 concentrations. This suggests that a DBA-induced suppression in estradiol catabolism is present and may either involve a targeted effect on the estrogen binding site on the CYP2B1/2 and CYP1A genes apart from the PhB-responsive unit, or a second pathway (possibly sulfation) that is not PhB-inducible.

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 09/01/2003
Record Last Revised: 12/22/2005
Record ID: 75416

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

REPRODUCTIVE TOXICOLOGY DIVISION

ENDOCRINOLOGY BRANCH