Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

Abstract

Multiple exposures to the herbicide atrazine (ATRZ) were shown to suppress the LH surge in both cycling female rats and those ovariectomized (OVX) and primed with estradiol (E 2 ). A single ATRZ administration was found to induce a prompt and marked increase in progesterone (P 4 ). As exogenous P 4 is known to have a differential effect on the LH surge depending on its temporal relationship with the surge, it was hypothesized that a single treatment in an OVX, E 2 -primed rat would augment the surge, whereas several exposures would cause a decrease. Following four daily treatments with 100 mg/kg, LH surge was suppressed. In contrast, a single ATRZ exposure elevated the surge. Two treatments were without effect. The single administration caused a large increase in P 4 at 30 and 60 min that was likely attributable to adrenal secretion. Four exposures also elevated P 4 after the final treatment, although the duration of the increase was shortened. A single treatment with 0, 10, 30, and 100 mg/kg ATRZ showed similar elevations at the highest concentration in P 4 , the LH peak, and area under the curve (AUC), whereas four exposures reduced the AUC. An increase at 1 h in the expression of Kiss1 in the anteroventral periventricular nucleus suggests that this regional kisspeptin neuronal population has a role in the ATRZ augmentation of the surge. These data support the hypothesis that ATRZ-induced changes in adrenal P 4 can either augment or attenuate the surge depending on the temporal proximity of exposure to the rise in LH.

The Effect of Atrazine Administered by Gavage or in Diet on the LH Surge and Reproductive Performance in Intact Female Sprague‐Dawley and Long Evans Rats

“…Previously, we and others have shown that hormone-induced LH surges in ovariectomized rats could be reduced in magnitude with four daily bolus doses of ATR (Cooper et al, 2000; McMullin et al, 2004; Foradori et al, 2011). Recently, Goldman et al (2013) reported that four daily doses of ATR, administered by gavage, was required for ATR to inhibit LH surge. Interestingly, shorter treatment periods (after 1 dose) actually enhanced the LH surge, while 2 and 3 days of dosing had no effect (Goldman et al, 2013).…”

“…Recently, Goldman et al (2013) reported that four daily doses of ATR, administered by gavage, was required for ATR to inhibit LH surge. Interestingly, shorter treatment periods (after 1 dose) actually enhanced the LH surge, while 2 and 3 days of dosing had no effect (Goldman et al, 2013). The authors postulated that ATR works via the hypothalamic-pituitary-adrenal (HPA) axis to alter the LH surge.…”

“…The mechanism whereby ATR induced activation of the HPA axis leads to an inhibition of the LH surge is not known. However, the time- and dose-dependent differential effect of ATR on LH surge may be due to a transition from progesterone as a positive to negative feedback on the HPG axis (Caligaris et al, 1971; DePaolo and Barraclough, 1979; Wagenmaker et al, 2009; Goldman et al, 2013). …”

Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat

“…Goldman et al. (2013) showed that a single dose of 100 mg/kg ATZ administered 8 hr after lights‐on enhanced peak LH in estrogen‐primed, ovariectomized female Long Evans rats, whereas the LH surge was suppressed after the fourth daily dose of ATZ. In contrast, in an unpublished study from our laboratory, female SD rats administered 100 mg/kg ATZ immediately after lights‐on in a 14:10 light/dark cycle, displayed no effect on the LH surge on Day 1, indicating that ATZ administered before the “critical window of time” was incapable of enhancing the LH surge via HPA activation.…”

Toxic Effects of Atrazine on Reproductive and Immune Systems in Animal Models

“…The herbicide's impact on the lobster population is still not fully clear, but the herbicide could have possibly damaged the reproductive system of the lobsters. Previous studies shown that a commonly used herbicide, Atrazine, disrupts and damages the reproductive system across vertebrate classes [2][3][4][5][6]. These previous studies also found that Atrazine causes a reduction in androgen and an induction of estrogen within vertebrates [7,8], but few researchers have tested the effects and toxic concentrations of Atrazine on invertebrates [9].…”