Rapid steroid hormone actions via membrane receptors.
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.
Department of Otolaryngology, Meir Hospital, Kfar Saba, Israel.
Nofrat
N
Schwartz
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, United States.
Anjali
A
Verma
School of Art, Virginia Commonwealth University, Richmond, VA, United States.
Caroline B
CB
Bivens
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, United States; University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Zvi
Z
Schwartz
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, United States; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States. Electronic address: bboyan@vcu.edu.
Barbara D
BD
Boyan
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism*
D006728:Hormones; D011956:Receptors, Cell Surface; D013256:Steroids
Cancer; ERα36; Estrogen; Hormones; Membrane receptors; Vitamin D3