Structure and function of estrogen receptors

This chapter examines the structure and function of estrogen receptors. Steroid hormones, retinoids, thyroid hormone, and other small lipophilic hormones elicit numerous effects in mammalian cells and tissues by binding to receptors that function directly as ligand-dependent transcription factors. The estrogen receptor is a member of a superfamily of nuclear receptors that includes receptors not only for steroid and thyroid hormones and certain vitamins but also for many other proteins, referred to as “orphan receptors.” Estrogens stimulate the proliferation not only of normal cells in female sex accessory tissues but also of a number of cancers, including breast, endometrial, and ovarian cancers. In some cases, AP-1 activity is increased and in other cases it is decreased, the differential response depending on the composition of the AP-1 complex. In MCF-7 breast cancer cells, growth factor-induced AP-1 activity is increased by estrogens and reduced by antiestrogens. The first target genes to be identified and characterized were those that encode vitellogenin, ovalbumin, and apo-very low-density lipoprotein in oviparous vertebrates. © 1995, Academic Press Inc. All rights reserved.