Lactational Exposure of Atrazine and the role of Prolactin in the Development of the Adult Male TIDA Neuronal System.

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Title: Lactational Exposure of Atrazine and the role of Prolactin in the Development of the Adult Male TIDA Neuronal System.
Author: Langdale, Christopher Lawrence
Advisors: Dr. Gregory Cole, Committee Member
Dr. Ida Smoak, Committee Member
Dr. Ralph Cooper, Committee Co-Chair
Dr. Kenneth Adler, Committee Chair
Abstract: Previous studies by Stoker et al., (1999b) and Shyr et al., (1986) examined the role of the rat dam's prolactin (Prl) during lactation on subsequent development on the offspring. Shyr identified a critical role for milk-derived Prl in postnatal development of tuberoinfundibular dopamanergic neurons (TIDA) by dosing lactating dams with bromocriptine, a dopamine (DA) agonist, on postnatal day (PND) 2-5, and PND 9-12 to block the release of maternal Prl in the milk. Offspring deprived of milk Prl from PND 2-5 showed a decrease in DA concentration and turnover rate in the median eminence on PND 33-35, demonstrating the importance of Prl to normal TIDA development. Furthermore, this decrease in DA was associated with hyperprolactinemia in male offspring when serum concentrations were measured on PND 30-32. However, no disruption of the TIDA development was observed in dams dosed from PND 9-12, suggesting that PND 2-5 was a sensitive time point for normal development of TIDA neurons. Stoker et al., (1999b) found that exposure of the dam to atrazine during the first 4 days of lactation suppressed maternal suckling-induced prolactin release. Interestingly, this treatment also led to an increased incidence of lateral prostate inflammation in adult offspring. However, prostate inflammation was absent in the male offspring when the atrazine-treated dam was co-treated with ovine prolactin. These observations have led to the hypothesis that decreased maternal prolactin (following atrazine or bromocriptine exposure) will lead to impaired TIDA development and elevated levels of prolactin in the juvenile male offspring (as shown by Shyr et al., 1986 and Stoker et al., 1999b). The two basic assumptions of this hypothesis have yet to be examined and are the focus of this study. First, can an increase in the concentration of serum Prl be determined in male offspring of dams treated with atrazine during early lactation; and second, is there evidence of a decrease in TIDA neuronal activity (DA concentration and turnover) following atrazine exposure? The potential of this herbicide to affect hormones normally present in milk and transiently alter development of the human offspring may be of concern to human health. Lactating females were dosed from PND 1-9, twice a day with 12.5, 25, or 50 mg/kg atrazine or 0.209 mg/kg bromocritine (PND 1-5). Male pups were selected and killed two hours before lights were turned off (14:10 light cycle). Serum Prl and TIDA neuronal development results supported both basic assumptions. An increase in serum Prl in male offspring of both atrazine 12.5 mg/kg and bromocriptine-treated dams were identified on PND 12 and 35, which was also consistent with prior reports by Shyr et al. (1986). The increase in serum Prl also coincided with decreased TIDA neuronal activity on PND 35. However, a non-linear dose response was observed following atrazine exposure to the dam in both brain aminergic and serum Prl concentrations in the offspring. Also, both compounds caused significant changes in the developmental profiles of dopamine and dopaminergic activity in all three brain areas tested. Although the atrazine data revealed a non-linear dose response in the offspring, the fact that the lowest dose of this herbicide produced changes that were similar to the positive control suggests that indeed this complex mode of action is affected by atrazine-treatment. Due to the complexity of the maternal-neonatal unit, subsequent studies examining the offspring at a later age will be required.
Date: 2004-04-21
Degree: MS
Discipline: Comparative Biomedical Sciences

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