Characterization of Sex Hormone Binding Protein Alpha-Fetoprotein Production during Natural Sexual Differentiation and Endocrine Disruption

Presentation Number: SAT 258
Date of Presentation: April 1st, 2017

Joshua Philip Mogus*, Ciro Maurizio Amato and Krista Mccoy
East Carolina University, Greenville, NC

Abstract

The correct milieu, concentration, and timing of exposure to sex hormones are essential for normal development of sexually dimorphic tissue structure and function (e.g., penis vs. vagina). Alpha-1-fetoprotein (AFP), is a sex steroid binding protein produced by the fetal liver, that binds circulating estrogens with high affinity, regulating its transport to tissues. Despite its necessity for fetal steroid regulation, AFP has not been quantified throughout sexual differentiation in the mouse model, which limits our ability to fully understand and characterize the role that endogenous sex hormones play in sexual dimorphic development. In addition, a number of pollutants, called endocrine disrupting chemicals (EDCs), are known to alter steroidogenesis and receptor-ligand interactions. However, the way in which transport proteins, like AFP are altered by EDC exposure remains relatively unexplored. To address these deficits, we quantify fetal liver AFP concentrations, and bound and free sex hormone concentrations in the mouse via validated ELISAs during sexual differentiation (embryonic days (E) 14.5-17.5). In addition, we exposed pregnant dams during this same time period to the model EDC Vinclozolin (125mg/kg) and quantify liver AFP, and sex hormone concentrations in male and female fetuses at E17.5. We characterize sex specific AFP concentrations across time and between control and Vinclozolin exposed embryos and directly link AFP quantity with bound vs. free sex hormone concentrations. Understanding the dynamic nature between AFP and sex hormone binding across time in males and females as well as how these relationships are altered by EDCs will provide foundational information that will help redefine the mechanisms through which pollutants can alter endocrine function.

 

Nothing to Disclose: JPM, CMA, KM