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An Estrogen Receptor (ER) Deoxyribonucleic Acid-Binding Domain Knock-In Mutation Provides Evidence for Nonclassical ER Pathway Signaling in Vivo

Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: J. Larry Jameson, M.D., Ph.D., Department of Medicine, Northwestern University Medical School, 251 East Huron Street, Galter 3-150, Chicago, Illinois 60611. E-mail: ljameson{at}northwestern.edu.

We created a nonclassical estrogen receptor (ER) knock-in mouse model by introducing a mutation that selectively eliminates classical ER signaling through estrogen response elements, while preserving the nonclassical ER pathway. Heterozygous nonclassical ER knock-in (NERKI) females are infertile. Their ovaries contain no corpora lutea, reflecting a defect in ovulation, and the stromal cells contain lipid droplets, suggesting altered steroidogenesis. The uteri are enlarged with evidence of cystic endometrial hyperplasia, and the mammary glands are hypoplastic. These phenotypic features indicate differential ER effects on growth and development in various estrogen-responsive tissues. These findings suggest that nonclassical ER signaling pathways play an important physiological role in the development and function of the reproductive system.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα

Ligands:   17β-Estradiol  |  Progesterone

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