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

Mol Endocrinol. 2002 Oct;16(10):2188-201. doi: 10.1210/me.2001-0174.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • DNA / metabolism*
  • Endometrial Hyperplasia / genetics
  • Endometrial Hyperplasia / pathology
  • Estrogen Receptor alpha
  • Female
  • Heterozygote
  • Hormones / pharmacology
  • Infertility, Female / genetics*
  • Infertility, Female / physiopathology
  • Male
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Mutant Strains
  • Mutation*
  • Ovary / drug effects
  • Ovary / physiopathology
  • Ovulation / genetics
  • Ovulation Induction / methods
  • Progesterone / blood
  • Prolactin / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Response Elements / genetics
  • Signal Transduction*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Uterus / abnormalities
  • Uterus / pathology
  • Zinc Fingers

Substances

  • Estrogen Receptor alpha
  • Hormones
  • Receptors, Estrogen
  • Transcription Factor AP-1
  • Progesterone
  • Prolactin
  • DNA