Alcohol was recently listed as a direct cause of breast cancer, though the mechanisms underlying this effect are unknown. Moreover, how alcohol interacts with endocrine-disrupting agents (EDCs), like plastic products that store it, is understudied. Our lab has shown a synergistic effect of adolescent alcohol and phthalate co-consumption on mammary gland development. The hypothalamus is a neural substrate responsible for regulating pubertal development and reproductive function. Thus, we hypothesized that disruptions to GABAergic signaling in the developing hypothalamus may lead to changes in hormone balance and atypical mammary gland growth. To evaluate this, we measured immunoreactivity of the delta subunit of the GABA receptor (GABRD), Gonadotropin Releasing Hormone (GnRH), Tyrosine Hydroxylase (TH), and NeuN in mice exposed to alcohol (20%), water, alcohol with DEHP (0.5%)
(Di-2-ethylhexyl phthalate), or no treatment. Tissues from each group of treated mice were analyzed to measure GABRD intensity. The intensity measurement for GABRD supported our hypothesis that exposure to ethanol and DEHP suppresses GABRD expression. The water group displayed significantly higher levels of GABARD expression than the non-drinking group. The differences between these control mice indicate a potential impact of handling on GABRD. Staining for GnRH, NeuN, and TH did not yield analyzable data due to either insufficient staining or high autofluorescence. The findings thus far support extra-mammary effects of alcohol and phthalates on GABAergic signaling, which could underlie vulnerability to abnormal mammary gland development following adolescent binge drinking and co-exposure to EDCs.
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