EFFECT OF 2,4-D EXPOSURE ON PUBERTAL DEVELOPMENT AND THYROID FUNCTION IN THE MALE WISTAR RAT

Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) is used extensively in agriculture as a herbicide and has been suspected to have endocrine disrupting activity. Because 2,4-D has been reported to alter CNS monoaminergic function, we hypothesized that it may also modify hypothalamic regulation of pituitarygonadal function. Therefore, we evaluated the effects of 2,4-D on pubertal development and thyroid function in the juvenile male Wistar rat. The rats were exposed to 0, 100 or 200 mg/kg of 2,4-D by oral gavage from postnatal day (PND) 23 to 53. Preputial separation (PPS) was evaluated beginning on PND 33. The rats were necropsied on PND 53 and tissue weights recorded. Serum was collected at necropsy and analyzed for thyroid, testicular and pituitary hormone concentrations. PPS was significantly delayed for 2.7 days in the 200 mg/kg group as compared to controls. However, no effect on PPS was observed at 100 mg/kg. The mean weight of the ventral prostate and levator ani plus bulbocavernosus muscles (LABC) was significantly decreased in the 200 mg/kg group. Testosterone and androstenedione were significantly decreased following exposure to the highest dose of 2,4-D, but luteinizing hormone and prolactin were not altered at either dose. Triiodothyronine (T3) and thyroxine (T4) were significantly decreased at both 100 and 200 mg/kg of 2,4-D. The altered pubertal onset and reduced growth of the androgen-dependent tissues appear to be the result of a suppression of the androgenic hormones. Further studies are needed to determine if the pubertal alterations are due to changes in the CNS regulation of pituitarygonadal function or to direct effects on testicular function. This abstract does not necessarily reflect EPA policy. (platform)