1

The Influence of 1, 2, and 4 Days of Atrazine Treatments on the 

LH Surge in Ovariectomized / Estradiol-primed Rats: 

Preliminary Report to the Office of Chemical Safety and Pollution Prevention

Jerome Goldman, Lori Davis, Ashley Murr and Ralph Cooper

Endocrine Toxicology Branch, Toxicity Assessment Division,

National Health and Environmental Effects Research Laboratory, ORD,

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

This internal report was prepared for the US EPA OCSPP and submitted on 28 April 2011

Disclaimer: This report has been reviewed in accordance with the policy of the National Health 

and Environmental Effects Research Laboratory, Office of Research and Development, U.S. 

Environmental Protection Agency and approved for dissemination. Approval does not signify 

that the contents necessarily reflect the views or policy of the Agency, nor does mention of 

trade names or commercial products constitute endorsement or recommendation for use.
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Introduction

Previous studies from our laboratory had shown that the chlorotriazine herbicide atrazine 

administered to cycling female rats for 4 consecutive days diminished the surge of luteinizing 

hormone (LH) from the pituitary that serves as the proximal trigger for ovulation (Fig. 1)

(Cooper et al., 2000; 2007). Perhaps the most compelling evidence supporting this finding is 

the fact that atrazine exposure alters the pulsatile release of gonadotropin releasing hormone 

(GnRH), the final common signal emanating from the brain to regulate LH release (Cooper et al., 

2007; Foradori et al., 2009). Recent studies from our laboratory on both the hypothalamicpituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes have continued to 

provide some insight into the sequence of neuroendocrine changes that take place following 

the initial exposure to this chemical and how these changes ultimately lead to a disruption of 

gonadal function. This includes the observation that atrazine (and atrazine metabolites) 

activates the HPA axis within minutes in both males (Laws et al., 2009) and females (Fraites et 

al., 2009). Below we discuss the effects of atrazine on these two broad neuroendocrine axes

and those events that lead to impaired LH secretion. 

As indicated, the accepted mode of action for the atrazine-induced impairment of LH secretion 

is a disruption in the central (CNS) mechanisms controlling LH release (i.e., impaired GnRH 

release) (Cooper et al., 2007; Foradori et al., 2009). Direct exposure of pituitary tissue in vitro 

did not affect LH secretion (Fig. 2). This central mode of action was reviewed by the 2003 

atrazine Science Advisory Panel and supported by research from several laboratories (McMullin 

et al., 2004; Foradori et al., 2009). However, there is little known about the exact molecular or 

neuronal events responsible for an atrazine-induced change in GnRH/LH release. It is assumed 

that the changes in GnRH occur as a result of either (1) a direct effect of the chlorotriazines on 

the GnRH neurons themselves (2) an effect of the herbicide on the neuronal mechanisms

known to regulate GnRH (and thus affect GnRH cellular activity indirectly) or (3) an effect on 

both the GnRH neurons and those neurons regulating GnRH activity. 
3

Recent studies revealed that atrazine (and exposure to atrazine metabolites) leads to a rapid 

(within minutes) increase in both adrenocorticotropin (ACTH) secretion and adrenal steroid 

hormone production (corticosterone and progesterone) in both male (Laws et al., 2009) and 

female (Fraites et al., 2009) rats. The rapidity of this dose-dependent, atrazine-induced HPA 

response, and the finding that this response can be initiated following intravenous injection 

with the atrazine metabolite desisopropylatrazine (DIA) (Fraites et al., 2009) suggested that 

atrazine activates the adrenal axis by targeting the CNS (putatively the hypothalamus) directly 

to alter the control of ACTH. In addition, other data (Fraites et al., 2009) indicated that it is 

unlikely that atrazine causes a non-specific stress response in the animal. The significance of 

these observations for interpreting the events leading to impaired LH secretion becomes clear 

when one considers the role of progesterone (both adrenal and ovarian) in the regulation of LH,

as well at the impact that an inappropriate exposure to corticosterone has on the HPG axis in 

general. 

Estradiol and progesterone have long been known to play coordinate roles in the generation of 

the surge (Mann & Barraclough, 1973). In a female rat exhibiting a normal 4-day estrous cycle, 

estradiol begins to rise on diestrus day 2, reaching a midday apex on the following day of 

proestrus. This increase serves to increase the responsiveness of the hypothalamic 

mechanisms that promote the secretion of GnRH into the hypothalamic-pituitary portal vessels 

and the subsequent surge of LH on the afternoon of proestrus. Progesterone, on the other 

hand, shows a rise beginning around noontime on proestrus and acts synergistically with 

estradiol to generate a surge (Brown-Grant and Naftolin, 1972). This effect of progesterone in 

combination with estradiol is clearly demonstrated in the ovariectomized rat (Fig. 3). 

Progesterone treatment alone in these females is without effect on the induction of a surge 

(e.g., Caligaris et al., 1971). In contrast to the synergistic effect of progesterone, longer 

exposures are essentially inhibitory (e.g., Caligaris et al., 1971; Banks & Freeman, 1978; 1980;

Prilusky et al., 1984). In fact, LH in general and the ovulatory surge of LH in particular are

suppressed by extended elevations in progesterone and other progestins. This is the basis for 

the action of many oral contraceptives. Furthermore, increased levels of progesterone during a 

woman’s pregnancy, secreted first from the ovaries and subsequently from the placenta, 
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prevent the appearance of a surge and ovulation over that time. Finally, it is noteworthy that 

treatment with progestins also lowers serum gonadotropins and testosterone production in 

men (e.g., Amory, 2004) and in combination with a synthetic androgen has promise as a male 

hormonal contraceptive (Roth and Amory, 2011). Similarly, extended exposures to 

corticosterone also impair normal hypothalamic-pituitary-gonadal function. This biphasic effect 

of progesterone on the LH surge suggests that the effectiveness of atrazine in modifying LH 

secretion depends not only on the dosage administered, but also on the duration of exposure

prior to the appearance of the surge. Thus, we hypothesized that a single dose of atrazine 

(which increases adrenal progesterone secretion in the ovariectomized rat) administered on the 

expected day of the estrogen-induced LH surge would increase the amount of LH released 

(peak amplitude and area under the curve). In contrast, we also hypothesized that multiple 

days of exposure will suppress both the peak height of the surge and the amount of LH secreted 

as a result of the atrazine-induced daily increase in both progesterone and corticosterone. 

Materials and methods

a. Animals

Upon arrival, 60-day-old Sprague–Dawley female rats (Charles River Labs, Raleigh, NC) were 

provided with food/water ad libitum and acclimated to their new surroundings. They were 

housed under a 14-h light:10-h dark photoperiod (lights on 0500 h) with controlled 

temperature (22 ± 2 0C) and humidity (40–50%). Vaginal lavages were taken daily for 2 weeks to 

determine cycling status, and any non-cycling animals were eliminated from the study. All 

experimental procedures conformed to NIH standards for laboratory animal research and were 

approved by the Animal Care and Use Committee at the National Health and Environmental 

Effects Research Laboratory.

b. Dosing Materials

Atrazine (97.1% purity) was a gift from Syngenta Crop Protection, Inc. (Greensboro, NC). It was 

administered by oral gavage in a suspension of 1% methyl cellulose (M-7140, Sigma Chemical 

Co., St. Louis, MO) in reverse osmosis-purified deionized water. The dosing volume was 5.0 ml / 
5

kg body weight. The dose selected (100 mg/kg) was based upon previous results (Fig. 4) using 

an ovariectomized (OVX)/ estradiol-primed animal model that showed a complete suppression 

of the LH surge in response to three daily treatments at this concentration. Control animals 

received 1% methyl cellulose vehicle (5.0 ml / kg body weight). 

c. Experimental Procedures

Previously cycling rats were bilaterally OVX under ketamine/xylazine anesthesia and 

subcutaneously implanted with a 6 mm silastic capsule containing estradiol benzoate (4 mg/ml 

in sesame oil) to induce a daily surge of LH (Legan et al., 1975). Capsules were soaked in saline 

prior to implantation to preclude an initial uneven rise in circulating concentrations before they 

would fall to a relatively constant level. Three days after surgery, ~250 l aliquots of blood 

were gently expressed from a nick in a lateral tail vein into small serum separation tubes at 

1400, 1600 and 1800 h. The animals were then killed at 2000h and trunk blood taken. On the 

day blood was sampled, all animals were dosed at 1300h. One group received treatment only 

on that day. A second group was treated daily for 2 consecutive days, while a third was dosed 

for 4 days beginning just prior to ovariectomy. This experimental paradigm is shown in Figure 

5.

d. Hormonal Assays

Sera from all time points were analyzed for LH by radioimmunoassay using materials obtained 

from the National Hormone and Peptide Program through Dr. A.F. Parlow (University of 

California-Los Angeles Medical Center, Torrance, CA). Tracer iodination with 125I was 

performed in-house using chloramine-T, and each labeled hormone was separated from 

unreacted iodide by gel filtration chromatography. The assays were carried out according to 

recommendations accompanying each kit, with the sensitivity optimized by a 24 h coincubation of sample and first antibody prior to the addition of 125I -labeled tracer. Goat antirabbit gamma-globulin (Calbiochem, San Diego, CA) was used as second antibody. All samples 

were run in duplicate and included in a single assay, with a sensitivity of 0.11 ng/ml, and an 

5.8% intra-assay coefficient of variation.
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Serum progesterone (all sampling times) and estradiol (2000h) were analyzed in duplicate using 

antibody-coated tube kits purchased from Siemens Healthcare Diagnostic (Deerfield, IL). The 

sensitivities were 0.08 ng/ml (progesterone) and 10 pg/ml (estradiol). Intra-assay coefficients 

of variation were less than 10% for both steroid hormones.

e. Statistical Analyses

Serial LH samples were analyzed by a repeated measures analysis of variance (SAS 9.1, Cary, 

NC). Because the time of appearance of a surge peak can vary among animals (in our studies at 

the 1600 or 1800h sampling times), the four LH values for each animal were shifted along the 

horizontal axis so that analyses could be performed on the peaks (or highest LH 

concentrations), along with times designated as -6, -4, -2, +2, +4, and +6 hours from the peak. 

Sampled progesterone concentrations were also analyzed by a repeated measures analysis of 

variance (SAS 9.1, Cary, NC). Areas under the curve (AUC) for the sampling times were 

determined using MedCalc software (Mariakerke, Belgium), and the data for the different 

dosing regimens analyzed by t-test. Estradiol concentrations were analyzed by analysis of 

variance. Statistical significance was set at p < 0.05 for all statistical tests. 

Results

Figure 6 shows the progesterone response to dosing at the four sampling times. For animals 

receiving only a single dose, a statistically significant elevation is present at 1400h, 1 hour after 

atrazine treatment, but thereafter concentrations are comparable to the control group. 

However, after 4 days of daily exposures no differences were present at any of the sampling 

times, results that were comparable to those seen after 2 days of dosing (data not shown). No 

differences in estradiol from the implanted capsules were seen in trunk blood taken at 2000h

(Fig. 7). For LH, 4 days of dosing caused a significant suppression in peak height and AUC

through the serial samplings (Fig. 8). In response to two daily treatments, peak height was not

significantly diminished, although AUC remained decreased. The single administration of 
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atrazine, on the other hand, caused a marked and statistically significant elevation in both the 

peak height of the surge and AUC, the latter value was 184% over the control AUC.

Discussion

The disparity in the influence of a single vs. multiple daily doses of atrazine on the LH surge is 

likely attributable to an influence of this herbicide on adrenal progesterone and perhaps 

corticosterone secretion. This conclusion is based on what is known about the nature of the 

temporal relationships between these two adrenal steroids and the surge. From the data 

reported by Fraites et al. (2009), atrazine was able to induce a rapid elevation in progesterone 

to approximately 19 ng/ml just 15 minutes after a single 75 mg/kg exposure (greater than 4-

fold over controls) (Fig. 9). Although in the present work, we did not observe a significant 

difference from controls at 1 hour following the 2nd or 4th daily treatments, it is likely that 

progesterone was elevated prior to this time. At 15 minutes after the last of 4 daily atrazine 

doses, Fraites found that progesterone, while statistically significant at 7 ng/ml, was down to 3-

fold over controls, providing evidence of a decline in the stimulation of the adrenal 

progesterone response with multiple exposures. It would appear then that in the present 

experiment, the lack of a statistically significant atrazine-induced increase may well be due to a 

reduction in the magnitude of the rapid increase in progesterone, so that by 1 hour circulating 

levels have been sufficiently cleared to approach control concentrations.

Because progesterone and corticosterone are co-secreted from the adrenals, both steroids may 

have contributed to a combined effect on the LH surge. However, it appears unlikely that an 

increase in blood concentrations of corticosterone was involved in the 1 day effect on the 

surge, since previous data obtained employing this OVX / estradiol-primed animal model 

showed no difference in the surge when a single injection of corticosterone was given 5 hours 

prior to the anticipated LH peak (Fig. 10). In contrast, corticosterone administration on the 

previous day produced a statistically significant attenuation in LH, indicating that in the present 

experiments a combination of both adrenal steroids, along with a possible non-steroid-linked 

mode of action, could have induced the observed response to multiple atrazine dosages. 
8

From what is known about the relationships between estradiol and progesterone on the 

temporal course of facilitation and inhibition of the LH surge, it doesn’t seem that the present 

effects of atrazine are attributable to changes in circulating estradiol. Although Sanderson et al. 

(2000) found that estradiol concentrations were elevated following in vitro exposures of the 

H295R adrenocortical tumor cells to atrazine, this effect was due to an augmentation in 

synthesis through an increase in aromatase activity. In the present experiment, estradiol is 

exogenously provided via implant, and the concentration should remain consistent within a 

defined range.

In summary, the principal findings of this preliminary report demonstrate two important factors 

concerning the HPA/HPG interactions. First, a single dose of atrazine does affect the adrenal 

axis by increasing the amount of LH secreted during the afternoon LH surge. The fact that this 

same single dose of atrazine increases adrenal hormone secretion (primarily progesterone) 

would explain the enhancement of the surge. Second, multiple (four daily) doses of atrazine 

resulted in a suppression of the LH surge. Again, we attribute this ultimate suppression of the 

surge to the activation of adrenal hormone secretion following each dose of atrazine. As 

discussed above, the effect of continued exposure to both progesterone and corticosterone on 

LH secretion in general and on the LH surge in particular is well known. Although this 

preliminary study employed ovariectomized animals and a single dose of atrazine, it 

demonstrates that the changes in LH secretion can be predicted by a recognition of the capacity 

of this herbicide to affect adrenal steroid hormone production and the temporal impact of 

these steroids on LH. These data, when considered in combination with those results 

describing the hypothalamic response to atrazine exposure, depict a complex relationship 

between the HPG and HPA axes in the initiation of a cascade of neuroendocrine changes that 

ultimately lead to altered ovarian function. 
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References

.

Amory JK. Testosterone/progestin regimens: a realistic option for male contraception? (2005). 

Curr Opin Investig Drugs. 5:1025-1030.

Banks, JA, Freeman, ME. (1978). The temporal requirement of progesterone on proestrus for 

extinction of the estrogen-induced daily signal controlling luteinizing hormone release in the 

rat. Endocrinology 102:426-432.

Banks, JA, Freeman, ME. (1980). Inhibition of the daily LH release mechanism by progesterone 

acting at the hypothalamus. Biol. Reprod. 22:217-222.

Brown-Grant, K, Naftolin, F. (1972). Facilitation of LH secretion in the female rat by 

progesterone. J. Endocrinol. 53:37-46.

Cooper, RL, Stoker, TE, Tyrey, L, Goldman, JM, McElroy, WK. (2000). Atrazine disrupts the 

hypothalamic control of pituitary-ovarian function. Toxicol. Sci. 53:297-307.

Cooper, RL, Laws, SC, Das, PC, Narotsky, MG, Goldman, JM, Tyrey, EL, Stoker, TE. (2007). 

Atrazine and reproductive function: Mode and mechanism of action studies. Birth Def. Res., pt. 

B. 80: 98-112.

Fraites MJ, Cooper RL, Buckalew A, Jayaraman S, Mills L, Laws SC. (2009). Characterization of 

the hypothalamic-pituitary-adrenal axis response to atrazine and metabolites in the female 

rat.Toxicol. Sci. 112:88-99.

Foradori CD, Hinds LR, Hanneman WH, Legare ME, Clay CM, Handa RJ. (2009). Atrazine inhibits 

pulsatile luteinizing hormone release without altering pituitary sensitivity to a gonadotropinreleasing hormone receptor agonist in female Wistar rats. Biol Reprod. 81:40-45.

Goldman, JM, Cooper, RL. (2010). The impact of centrally acting pesticidal/environmental 

toxicants on the neuroendocrine regulation of reproductive function in the female rodent: 

relevance to human reproductive risk assessment. In: JC Eldridge, JT Stevens (Eds.), Endocrine 

Toxicology (3rd edition). Informa Healthcare: London. pp. 210-239.

Laws ̧ SC, Hotchkiss, M, Ferrell, J, Jayaraman, S, Mills, L, Modic, W, Tinfo, N, Fraites, M, Stoker, 

T, Cooper, R. (2009) Chlorotriazine herbicides and metabolites activate an ACTH-dependent 

release of corticosterone in male Wistar rats. Toxicol. Sci. 112:78-87.
10

Legan, SJ, Coon, GA, Karsch, FJ (1975). Role of estrogen as initiator of daily LH surges in the 

ovariectomized rat. Endocrinology 96:50-56.

Mann, DR, Barraclough, CA. (1973). Role of estrogen and progesterone in facilitating LH release 

in 4-day cyclic rats. Endocrinology 93:694-699.

McMullin, TS, Andersen, ME, Nagahara, A, Lund, TD, Pak, T, Handa, RJ, Hanneman, WH. (2004). 

Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced 

surge of luteinizing hormone in female Sprague-Dawley rats without changing estrogen 

receptor action. Toxicol. Sci. 79:278-286.

Prilusky, J, Vermouth, NT, Deis, RP. (1984). A dual modulatory effect of progesterone on the 

LHRH-induced LH release. J. Steroid. Biochem. 21:107-110.

Roth, MY, Amory, JK. (2011). Pharmacologic development of male hormonal contraceptive 

agents. Clin. Pharmacol. Ther. 89:133-136.

Sanderson JT, Seinen W, Giesy JP, van den Berg M. (2000). 2-Chloro-s-triazine herbicides induce 

aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: a novel mechanism 

for estrogenicity? Toxicol. Sci. 54:121-127.
11

Figure 1. Mean (+ SEM) concentrations of LH during the afternoon of vaginal proestrus in 

confirmed regularly cycling rats dosed with atrazine (mg/kg) by gavage at 12:00 hr for 4 

consecutive days. * p<0.05 versus control at same time point (from Cooper et al. Birth Defects 

Res. (Part B), 80:98-112, 2007).
12

Fig. 2. 100 M atrazine has no effect on LH secretion from the pituitary when tested in vitro. 

Control and treated pituitary fragments were incubated for 2.5 hr and then exposed to two 

pulses of GnRH (85 nM) followed by a KCI challenge (60 mM). LH release was not different at 

any of the time points examined (from Cooper et al. Atrazine disrupts the hypothalamic 

control of pituitary-ovarian function. Toxicol Sci 53:297–307, 2000)
13

ng LH / ml Serum

40

0

-6 -4 -2 Peak +2 +4 +6

Hours from Peak

30

20

10

OVX- Estradiol Implant / SQ Progesterone

6

5

4

3

2

1

0

-6 -4 -2 Peak +2 +4 +6

Hours from Peak

OVX- Implanted Estradiol Capsule

Figure 3. Influence of a subcutaneous (SQ) injection of progesterone on an LH surge in 

ovariectomized rats implanted with an estradiol capsule at the time of surgery. Small aliquots 

of tail blood were removed over the afternoon of the third day after ovariectomy in rats with 

or without a SQ injection of progesterone (2.5 mg/0.2 ml sesame oil) administered just prior to

serial sampling for LH (Goldman et al., 2010). Concentrations are indicated in ng/ml + SEM. 

Progesterone given alone at that time would be unable to elicit a surge.
14

Figure 4. The influence of three daily oral atrazine treatments on the LH surge in 

ovariectomized / estradiol-primed rats. Trunk blood was taken from animals killed at 0, 1, 3 

and 6 hours after the last 1300h dosing. *p<0.05 compared to the 0 mg/kg control group at the 

same time point.

0 50 100 200 300

0

1

2

3

4

5

0 1 3 6 0 1 3 6 0 1 3 6 0 1 3 6 0 1 3 6

Luteinizing Hormone (ng/ml)

Time (h)

Dose (mg/kg)

OVX / E2-prime

3 Daily Doses (1300h)

Cooper et al. Toxicol Sci. 53:297 (2000)

* * * * *

* * * * * *
15 O

V

X

d0 d1 d2 d3 Samples

Atrazine / Vehicle

O

V

X

d0 d1 d2 d3 Samples

Atrazine / Vehicle

O

V

X

d0 d1 d2 d3 Samples

Estradiol Capsule

Estradiol Capsule

Estradiol Capsule

Atrazine / Vehicle

Atrazine / Vehicle Atrazine / Vehicle Atrazine / Vehicle Atrazine / Vehicle

Figure 5. Study design using the ovariectomized / estradiol-primed model. Estradiol implants are 

inserted at the time of ovariectomy (OVX), releasing the hormone over the ensuing 3 days (horizontal 

arrows). Oral exposures to methylcellulose vehicle or 100 mg/kg atrazine are administered for 1, 2, or 4 

days at 1300h (vertical arrows), and serial blood samples are taken at 1400, 1600, 1800, and 2000h

(green triangles). The white and shaded boxes indicate the light:dark portions of the photoperiod.
16

1400 1600 1800 2000

2

3

4

5

6

7

8

9

10

11

12

0

100

1 day

Serum Progesterone (ng/ml)

Time of Day

**

1400 1600 1800 2000

2

3

4

5

6

7

8

9

10

11

12

0

100

4 days

Serum Progesterone (ng/ml)

Time of Day

Figure 6. Serum concentrations of progesterone (ng/ml + SEM) over the sampling times for the 

1- and 4-day atrazine (0 and 100 mg/kg) exposures. **P<0.01 for the difference between the 

two doses at that time.
17

1d

2d

4d

0

20

40

60

80

0

100

100

Serum Estradiol (2000h) pg/ml

Ovariectomized / E2-prime

Atrazine

mg/kg

Days of Treatment

Figure 7. Serum estradiol concentrations (pg/ml + SEM) for the treatment groups determined 

at the 2000h sampling time.
18

-4 -2 Peak +2 +4 +6

0

2

4

6

8

10

12

Ovariectomized / E2 prime - Atrazine 4 Days

Serum LH (ng/ml)

Time Relative to Peak

0

100

(10)

(10)

mg/kg

*

0

15

20

Serum LH (ng/ml)

Area Under the Curve

4 Days Dosing Atrz (1300h)

sampling 1400-1600-1800-2000h

OVX / E2-implant

Atrazine (mg/kg)

0 100

*

55%

10

5

-4 -2 Peak +2 +4 +6

0

2

4

6

8

10

12

Ovariectomized / E2 prime - Atrazine 2 Days

Serum LH (ng/ml)

0

100

(9)

(8)

mg/kg

Time Relative to Peak

0

5

25

30

Serum LH (ng/ml)

Area Under the Curve

2 Days Dosing Atrz (1300h)

sampling 1400-1600-1800-2000h

OVX / E2-implant

Atrazine (mg/kg)

0 100

*

56%

20

15

10

-4 -2 Peak +2 +4 +6

0

2

4

6

8

10

12

Ovariectomized / E2 prime - Atrazine 1 Day

Serum LH (ng/ml)

Time Relative to Peak

0

100

(11)

(11)

mg/kg

**

*

0

50

0 100

Serum LH (ng/ml)

Area Under the Curve

1 Day Dosing Atrz (1300h)

sampling 1400-1600-1800-2000h

OVX / E2-implant p=0.012

*

(1-tailed)

Atrazine (mg/kg)

184%

40

30

20

10

Figure 8. The LH surge (ng/ml + SEM) and areas under the curve in response to 4, 2 and 1 day 

of atrazine treatment. The numbers in parentheses indicate the group sizes for each of the 

treatments. The numbers within the 100 mg/kg columns at the right indicate the percent 

change from the 0 mg/kg group. *p<0.05, **p<0.01
19

0

5

10

15

20

25

Progesterone (ng/ml)

vehicle ATR- 75 mg/kg

Redrawn from: Fraites et al. Toxicol. Sci. 112:88 (2009) 

Single Oral Exposure

15 min. post-dosing

0

5

10

15

20

25

vehicle ATR- 75 mg/kg

4 Daily Exposures

15 min. after last dose

**

**

Figure 9. Comparison of the increase in progesterone (ng/ml + SEM) at 15 minutes in response 

to 1 and 4 daily exposures to 75 mg atrazine/kg. **p <0.01
20

-4 -2 0 +2 +4

0

0.5

1

1.5

2

2.5

3

Control

CORT (5h from Pk)

CORT (20h from Pk)

*

Luteinizing Hormone (ng/ml)

Hours from Peak Time

Serum CORT (1400h)

Control 148.6 + 65.8

(ng/ml)

CORT 5h 429.7 + 65.8

CORT 20h 224.1 + 45.5

CORT 10mg/rat

Goldman et al. Pharmacol. Toxicol. 68:131 (1991)

Figure 10. Influence on the LH surge of corticosterone administration (10 mg/rat) to 

ovariectomized / estradiol-primed rats at two different times, 5 or 20 hours prior to the 

anticipated surge peak. *p<0.05 vs. control group at that time.