Rapid steroid hormone actions via membrane receptors

Nofrat Schwartz, Anjali Verma, Caroline B. Bivens, Zvi Schwartz, Barbara D. Boyan

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects.

Original languageEnglish (US)
Pages (from-to)2289-2298
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1863
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • Cancer
  • ERα36
  • Estrogen
  • Hormones
  • Membrane receptors
  • Vitamin D3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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