Methoxychlor induces estrogen-like alterations of behavior and the reproductive tract in the female rat and hamster: Effects on sex behavior, running wheel activity, and uterine morphology

doi:10.1016/0041-008X(88)90012-9

Toxicology and Applied Pharmacology

Volume 96, Issue 3, December 1988, Pages 525-540

https://doi.org/10.1016/0041-008X(88)90012-9 Get rights and content

Abstract

The current investigation was designed to determine if the pesticide methoxychlor (M) mimicked the effects of estrogen in the brain and on behavior. Running wheel activity (RWA) and sex behaviors were evaluated in this study because the role of estrogen in the regulation of these behaviors has been thoroughly established. M exposure at 400 mg/kg/day (90% pure) induced high levels of acyclic RWA and persistent vaginal estrus in the female rats. Following ovariectomy (ovx), RWA declined precipitously in controls but remained at high levels in M-treated-ovx females. M also produced estrogen-like alterations of the uterine endometrial epithelium, the ovary, and growth after ovx. In another study, ovx female rats were dosed with M at 200 mg/kg/day and then with progesterone (P). P acts as an antiestrogen and specifically suppresses estrogen-induced RWA. P blocks the synthesis of estrogen receptors in the CNS and reproductive tract but does not lower RWA induced by nonestrogenic mechanisms. After 14 days of M administration RWA was increased fourfold over the ovx-oil-treated females. Subsequently, P injections reduced RWA levels far below those seen when the ovx-M-treated rats were injected with oil. The P-induced decline represents a 95% inhibition of the M-induced increase in RWA. Subsequently, M-treated-ovx rats and hamsters were injected with P and tested for their ability to display reproductive behaviors when paired with a stud male. Female sexual behaviors are induced by the administration of estrogen followed by progesterone. In this study the M-treated females displayed reproductive behaviors, in contrast to the oil-treated rats and hamsters. The observation that the high levels of RWA induced by methoxychlor treatment in ovx rats can be suppressed by concurrent progesterone injections demonstrates that the increase in RWA is due to the estrogenic effects of methoxychlor on the CNS. The fact that methoxychlor, followed by P injections, induces behavioral estrus in the rat and hamster extends this estrogenicity to other areas in the CNS.

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Methoxychlor induces estrogen-like alterations of behavior and the reproductive tract in the female rat and hamster: Effects on sex behavior, running wheel activity, and uterine morphology

Abstract

Biochem. Pharmacol.

Toxicol. Appl. Pharmacol.

Environ. Res.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Pharmacol Ther.

Toxicol. Appl. Pharmacol.

Horm. and Behav.

Physiol. Behav.

Toxicol. Appl. Pharmacol.

Chronic toxicity effects of methoxychlor on the reproductive system of the rat

Actions of ovarian steroid hormones

Assessment of pituitary function

The Toxicologist

Estradiol 17-b reduces number of ovulations in adult rats: Direct action on the ovary?

Biol. Reprod.

Inbred strains

Effects of early postnatal androgen and estrogen injections on the estrous activity cycles and mating behavior of rats

Anat. Rec.

Ses differences in sensitivity of food intake, body weight, and running-wheel activity to ovarian steriods in rats

J. Comp. Physiol. Psychol.