Interacting Quantitative Trait Loci Control Phenotypic Variation in Murine Estradiol-Regulated Responses

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Abstract
The steroid hormone estradiol (E2) elicits a spectrum of systemic and uterotropic responses in vivo. For example, E2 treatment of ovari- ectomized adult and sexually immature rodents leads to uterine leu- kocytic infiltration, cell proliferation, and organ growth. E2-regulated growth is also associated with a variety of normal and pathological phenotypes. Historically, the uterine growth response has been used as the key model to understand the molecular and biochemical mech- anisms underlying E2-dependent growth. In this study, genome ex- clusion mapping identified two quantitative trait loci (QTL) in the mouse, Est2 and Est3 on chromosomes 5 and 11, respectively, that control the phenotypic variation in uterine wet weight. Both QTL are linked to a variety of E2-regulated genes, suggesting that they may represent loci within conserved gene complexes that play fundamen- tal roles in mediating the effects of E2. Interaction and multiple trait analyses using the uterine leukocyte response and wet weight suggest that Est4, a QTL on chromosome 10, may encode an interacting factor that influences the quantitative variation in both responses. Our results show that E2-dependent responses can be genetically con- trolled and that a genetic basis may underlie the variation observed in many E2-dependent phenotypes. (Endocrinology 140: 556 -561, 1999)

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