Estrogen-like effects of the mammary carcinogen 7,12- dimethylbenz(α)anthracene on hypothalamic neuronal membranes

Abstract

Previous studies have shown that in Sprague-Dawley female rats, but not in Wistar females, the mammary carcinogen dimethylbenz(α)anthracene (DMBA) results in extended preovulatory prolactin and estradiol surges, associated with inhibition of preovulatory gonadotropin surges, and in the induction of mammary tumors. Because earlier studies of similar endocrine states have shown this to be linked to hypothalamic arcuate nucleus neuronal membrane organization, in this study freeze-fracture methodology was used to determine whether DMBA may affect the ultrastructure of the neuronal membrane in the arcuate nucleus. The effects of estradiol valerate and DMBA were studied on 55- to 60-day-old cycling females, in Sprague-Dawley and Wistar rats, 8 weeks after the treatment. DMBA alone (15 mg/rat by gastric intubation) resulted in a significant decrease in the numerical density of intramembrane protein particles (IMP) in Sprague-Dawley rats but not in Wistar rats. The SC injection of estradiol valerate (1 mg/rat) resulted in a significant decrease of IMP numbers in both strains of rats. Although the subcutaneous injection of DMBA alone (1 mg/rat) did not affect IMP numerical density in either strain, the same potentiated the effect of estradiol valerate (1 mg/rat) on IMP's in Sprague-Dawley but not in Wistar females. These results indicate that DMBA affects the organization of neuronal plasma membrane in the hypothalamus of Sprague-Dawley rats. Wistar females are insensitive to both the endocrine and neuronal membrane effects of DMBA. Estradiol affected neuronal membranes in both strains and potentiated DMBA's effect. It appears that the estrogen-sensitive mechanism of DMBA activation may be lacking in Wistar rats.