Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring.
The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), TIDA neuronal growth is impaired and elevated PRL levels are present in the prepubertal male. These observations, combined with the finding that alterations in PRL secretion (i.e., hyperprolactinemia) in the adult male rat have been implicated in the development of prostatitis, led us to hypothesize that early lactational exposure to agents that suppress suckling-induced PRL release would lead to a disruption in TIDA development, altered PRL regulation, and subsequent prostatitis in the male offspring. To test this hypothesis, suckling-induced PRL release was measured in Wistar dams treated twice daily with the herbicide atrazine (ATR, by gavage, on PND 1-4 at 0, 6.25, 12.5, 25, and 50 mg/kg body weight), or twice daily with the dopamine receptor agonist bromocriptine (BROM, sc, at 0.052, 0.104, 0.208, and 0.417 mg/kg); BROM is known to suppress PRL release. Similarly, atrazine has also been reported to suppress PRL in adult females. Serum PRL was measured on PND 3 using a serial sampling technique and indwelling cardiac catheters. A significant rise in serum PRL release was noted in all control females within 10 min of the initiation of suckling. Fifty-mg/kg ATR inhibited suckling-induced PRL release in all females, whereas 25 and 12.5 mg/kg ATR inhibited this measure in some dams and had no discernible effect in others. The 6.25 mg/kg dose of ATR was without effect. BROM, used here as a positive control, also inhibited suckling-induced PRL release at doses of 0.104 to 0.417 mg/kg, with no effect at 0.052 mg/kg. To examine the effect of postnatal ATR and BROM on the incidence and severity of inflammation (INF) of the lateral prostate of the offspring, adult males were examined at 90 and 120 days. While no effect was noted at 90 days of age, at 120 days, both the incidence and severity of prostate inflammation was increased in those offspring of ATR-treated dams (25 and 50 mg/kg). The 12.5 mg/kg ATR and the two highest doses of BROM increased the incidence, but not the severity, of prostatitis. Combined treatment of ovine prolactin (oPRL) and 25 or 50 mg/kg ATR on PND 1-4 reduced the incidence of inflammation observed at 120 days, indicating that this increase in INF, seen after ATR alone, resulted from the suppression of PRL in the dam. To determine whether or not there is a critical period for these effects, dams were dosed with 25 and 50 mg/kg on PND 6-9 and PND 11-14. Inflammation was increased in those offspring from dams treated on PND 6-9, but this increase was not significant. Dosing on PND 11-14 was without effect. These data demonstrate that ATR suppresses suckling-induced PRL release and that this suppression results in lateral prostate inflammation in the offspring. The critical period for this effect is PND 1-9.
Stoker
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Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA. Stoker.tammy@epa.gov
Robinette
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Cooper
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D000818:Animals; D000833:Animals, Suckling; D001280:Atrazine / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D003864:Depression, Chemical; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D007774:Lactation / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011472:Prostatitis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D012756:Sheep
D006540:Herbicides; D011388:Prolactin; D004247:DNA; D009195:Peroxidase; D001280:Atrazine