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Methoxychlor mimics the action of 17 beta-estradiol on induction of uterine epidermal growth factor receptors in immature female rats

Methoxychlor mimics the action of 17 beta-estradiol on induction of uterine epidermal growth factor receptors in immature female rats

Reproductive Toxicology 10(5): 393-399

Epidermal growth factor (EGF) and its receptor (EGF-R) have been implicated as mediators for estrogen induced cellular growth. This study examines whether the action of the estrogenic pesticide methoxychlor (MXC) parallels the action of 17 beta-estradiol (E2) on uterine EGF-R. Administration of 20 micrograms E2/sexually immature female rat increased 125I-EGF binding to membranes extracted from whole uteri 175% over endogenous levels, while 500 mg MXC/kg led to a 156% increase. E2 in both 20 and 40 micrograms/rat doses and 500 mg MXC/kg led to maximal stimulation over endogenous levels, 12-h posttreatment. Rats were treated with E2, MXC, or vehicle plus 100 micrograms actinomycin-D (ACT-D) or 100 micrograms cycloheximide (CYCLO) per rat to determine if mRNA transcription and translation are involved in the increased EGF-R binding following estrogenic treatment. Only ACT-D inhibited the estrogenic stimulation of EGF-R binding, resulting in a 44% decrease when given concurrently with E2 or MXC, suggesting transcription is required. Additionally, ACT-D decreased endogenous receptor levels by 55%. No other differences were detected. When EGF-R binding data were analyzed by the method of Scatchard, both E2 and MXC, at maximal dosages, elevated uterine EGF-R binding sites by over 200% after 12 h as measured by maximal binding (Bmax) with no significant difference in dissociation constant (Kd) values. These results demonstrate that both E2 and MXC can stimulate the number of EGF-R binding sites without significantly altering the receptor binding affinity (Kd). Further, this stimulation is time dependent and is affected by dose.

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Accession: 046676841

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PMID: 8888411

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