Sex steroid hormone receptors, their ligands, and nuclear and non-nuclear pathways

Abstract

The ability of a cell to respond to a particular hormone depends on the presence of specific receptors for those hormones. Once the hormone has bound to its receptor, and following structural and biochemical modifications to the receptor, it separates from cytoplasmic chaperone proteins, thereby exposing the nuclear localization sequences that result in the activation of the receptor and initiation of the biological actions of the hormone on the target cell. In addition, recent work has demonstrated new pathways of steroid signaling through orphan and cell surface receptors that contribute to more rapid, “non-nuclear” or non-transcriptional effects of steroid hormones, often involving G-protein-mediated pathways. This review will summarize some of these studies for estrogens, androgens and progestins

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

“…They are sequestered in cytosol as an inactive complex by binding to heat-shock proteins (Hsps); upon binding to ligand or hormone, the steroid receptor separates from Hsps, hormone-receptor complex dimerizes and translocates into the nucleus, binds to specific regions of DNA, and transactivates the target genes [3]. The receptors that lack AF-2 domain fail to recognize HREs and hence do not mediate genomic pathways involved in the expression of ligand-mediated responses.…”

Is testosterone important in LUT function in men and women? ICI‐RS 2015

“…A G proteincoupled estrogen receptor (GPER) has been reported to mediate rapid E2 signaling which includes changes in intracellular calcium levels. 5 T also has rapid, transcription-independent (non-genomic) effects that are also mediated by a G-protein coupled receptor, recently described as GPCR6A. 6 Androgen and estrogen receptors are widely expressed throughout the body inclusive of tissues of the lower urinary tract (LUT) in adult females 7 and males, 7,8 as well as children (this study reports on males only 9 ).…”

“…Sex hormone signaling is mediated through binding to androgen receptors (AR) and estrogen receptors (ERa and ERb) located within the cell, easily accessed by the membrane permeable steroids. Ligand activated receptors then translocate to the nucleus where they bind to specific sites on DNA, 5 and thus can regulate the expression of a wide number of genes. In addition, androgens and estrogens are known to have acute (seconds to minutes) responses involving receptor activation at the level of the cell membrane often referred to ''non-genomic'' or non-nuclear steroid hormone signaling.…”

Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF‐7 Breast Cancer Cells to Tamoxifen

“…Hormone receptor positive (HR+) breast cancers represent 70% of all breast tumors. Their oncogenesis is a multiple step process thought to be driven by two transcription factors, the estrogen receptor (ER) and/or the progesterone receptor (PR) . Consequently, the endocrine‐targeted therapeutic approach has focused on both receptors as prognostic markers and therapeutic targets, aiming to alter the estrogen signaling for patients with ERα‐positive disease…”

“…Their oncogenesis is a multiple step process thought to be driven by two transcription factors, the estrogen receptor (ER) and/or the progesterone receptor (PR). [1] Consequently, the endocrinetargeted therapeutic approach has focused on both receptors as prognostic markers and therapeutic targets, [2] aiming to alter the estrogen signaling for patients with ERα-positive disease. [3] Over the past four decades tamoxifen (Tam) has been extensively used in neoadjuvant and adjuvant settings for the treatment of hormonal dependent breast cancers by acting as a competitive inhibitor of ER.…”