Differential regulation of Estrogen Receptor (ER)α and ERβ in primate mammary gland

Guojun Cheng, Yan Li, Yoko Omoto, Yanling Wang, Tove Berg, Magnus Nord, Pirkko Vihko, Margaret Warner, Yun Shang Piao, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Estrogen, mainly estradiol (E2), and progesterone (P) are essential for the growth and differentiation of the breast, but their roles in breast cancer are highly debated. To understand how E2 and P influence cell proliferation and differentiation, it is essential to know how their receptors are regulated. Because of limited tissue availability, little is known about regulation of the two estrogen receptors (ERα and ERβ) and the two progesterone receptor isoforms (PR-A and PR-B) in the normal human breast. What we know comes from rodent studies, which are not always pertinent for the human breast. We report now on regulation of gonadal hormone receptors during the menstrual cycle, pregnancy, and lactation in rhesus monkey mammary gland and on the relationship of these receptors to proliferation. We found that ERα but not ERβ is down-regulated when E2 levels increase and when cells enter the cell cycle. PR-B but not PR-A is expressed in proliferating cells. Thus under normal conditions, the ratio of ERα to ERβ in the breast depends on plasma concentrations of E2. Elevated expression of ERα (as occurs in postmenopausal women) is a normal response to loss of E2 and indicates non-proliferating cells. As selective receptor ligands become available, they will be helpful in delineation of the functions of these receptors.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number1
DOIs
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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