scholarly journals Steroid signal transduction activated at the cell membrane: from plants to animals.

2002 ◽  
Vol 49 (3) ◽  
pp. 735-745 ◽  
Author(s):  
Ewa Marcinkowska ◽  
Antoni Wiedłocha
Keyword(s):  
Cell Surface ◽  
Steroid Hormones ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Steroid Receptors ◽  
Transmembrane Protein ◽  
Steroid Receptor ◽  
Membrane Receptors ◽  
Protein Kinase Activity ◽  
Animal Cells

Steroid hormones in plants and in animals are very important for physiological and developmental regulation. In animals steroid hormones are recognized by nuclear receptors, which transcriptionally regulate specific target genes following binding of the ligand. In addition, numerous rapid effects generated by steroids appear to be mediated by a mechanism not depending on the activation of nuclear receptors. Although the existence of separate membrane receptors was postulated many years ago and hundreds of reports supporting this hypothesis have been published, no animal membrane steroid receptor has been cloned to date. Meanwhile, a plant steroid receptor from Arabidopsis thaliana has been identified and cloned. It is a transmembrane protein which specifically recognizes plant steroids (brassinosteroids) at the cell surface and has a serine/threonine protein kinase activity. It seems that plants have no intracellular steroid receptors, since there are no genes homologous to the family of animal nuclear steroid receptors in the genome of A. thaliana. Since the reason of the rapid responses to steroid hormones in animal cells still remains obscure we show in this article two possible explanations of this phenomenon. Using 1,25-dihydroxyvitamin D(3) as an example of animal steroid hormone, we review results of our and of other groups concordant with the hypothesis of membrane steroid receptors. We also review the results of experiments performed with ovarian hormones, that led their authors to the hypothesis explaining rapid steroid actions without distinct membrane steroid receptors. Finally, examples of polypeptide growth factor that similarly to steroids exhibit a dual mode of action, activating not only cell surface receptors, but also intracellular targets, are discussed.

scholarly journals Molecular Characterization of Membrane Steroid Receptors in Hormone-Sensitive Cancers

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2999
Author(s):  
Mirco Masi ◽  
Marco Racchi ◽  
Cristina Travelli ◽  
Emanuela Corsini ◽  
Erica Buoso
Keyword(s):  
Nuclear Receptors ◽  
Drug Targets ◽  
Target Genes ◽  
Steroid Receptors ◽  
Endocrine Disrupting Chemicals ◽  
Membrane Receptors ◽  
Potential Candidate ◽  
Candidate Drug ◽  
Biologic Effects ◽  
Hormone Sensitive

Cancer is one of the most common causes of death worldwide, and its development is a result of the complex interaction of genetic factors, environmental cues, and aging. Hormone-sensitive cancers depend on the action of one or more hormones for their development and progression. Sex steroids and corticosteroids can regulate different physiological functions, including metabolism, growth, and proliferation, through their interaction with specific nuclear receptors, that can transcriptionally regulate target genes via their genomic actions. Therefore, interference with hormones’ activities, e.g., deregulation of their production and downstream pathways or the exposition to exogenous hormone-active substances such as endocrine-disrupting chemicals (EDCs), can affect the regulation of their correlated pathways and trigger the neoplastic transformation. Although nuclear receptors account for most hormone-related biologic effects and their slow genomic responses are well-studied, less-known membrane receptors are emerging for their ability to mediate steroid hormones effects through the activation of rapid non-genomic responses also involved in the development of hormone-sensitive cancers. This review aims to collect pre-clinical and clinical data on these extranuclear receptors not only to draw attention to their emerging role in cancer development and progression but also to highlight their dual role as tumor microenvironment players and potential candidate drug targets.

Progesterone interaction with sperm plasma membrane, calcium influx and induction of the acrosome reaction

1999 ◽  
Vol 7 (2) ◽  
pp. 81-93 ◽  
Author(s):  
Christopher Bray ◽  
Jackson CK Brown ◽  
Steve Publicover ◽  
Christopher LR Barratt
Keyword(s):  
Plasma Membrane ◽  
Steroid Hormones ◽  
Nuclear Receptors ◽  
Acrosome Reaction ◽  
Calcium Influx ◽  
Membrane Receptors ◽  
Sperm Plasma Membrane ◽  
The Subject ◽  
Genomic Effects ◽  
Intense Research

In contrast to the classic action of steroid hormones through cytoplasmic/nuclear receptors, there is an accumulating body of data which strongly suggests that they have a direct effect on cells mediated through putative membrane receptors, a so-called non-genomic action. Although such non-genomic effects were discovered 50 years ago it is only in the last 15 years that the subject has become an area of intense research.

scholarly journals Adrenal and sex steroid receptor evolution: environmental implications

2001 ◽  
Vol 26 (2) ◽  
pp. 119-125 ◽  
Author(s):  
ME Baker
Keyword(s):  
Nuclear Receptors ◽  
Protein Interactions ◽  
Steroid Receptors ◽  
Sequence Divergence ◽  
Heat Shock Protein 90 ◽  
Steroid Receptor ◽  
Retinoid X Receptor ◽  
Sex Steroid ◽  
Environmental Implications ◽  
Sex Steroid Receptors

The nuclear receptor family responds to a diverse group of ligands, including steroids, retinoids, thyroid hormone, prostaglandins and fatty acids. Previous sequence analyses of adrenal and sex steroid receptors indicate that they form a clade separate from other nuclear receptors. However, the relationships of adrenal and sex steroid receptors to each other and to their ancestors are not fully understood. We have used new information from androgen, estrogen, mineralocorticoid and progesterone receptors in fish to better resolve the phylogeny of adrenal and sex steroid receptors. Sequence divergence between fish and mammalian steroid receptors correlates with differences in steroid specificity, suggesting that phylogeny needs to be considered in evaluating the endocrine effects of xenobiotics. Among the vertebrate steroid receptors, the most ancient is the estrogen receptor. The phylogeny indicates that adrenal and sex steroid receptors arose in a jawless fish or a protochordate and that changes in the sequence of the hormone-binding domain have slowed considerably in land vertebrates. The retinoid X receptor clade is closest to the adrenal and sex steroid receptor clade. Retinoid X receptor is noteworthy for its ability to form dimers with other nuclear receptors, an important mechanism for regulating the action of retinoid X receptor and its dimerization partners. In contrast, the adrenal and sex steroid receptors bind to DNA as homodimers. Moreover, unliganded adrenal and sex steroid receptors form complexes with heat shock protein 90. Thus, the evolution of adrenal and sex steroid receptors involved changes in protein-protein interactions as well as ligand recognition.

scholarly journals Minireview: The Versatile Roles of Lysine Deacetylases in Steroid Receptor Signaling

2014 ◽  
Vol 28 (5) ◽  
pp. 607-621 ◽  
Author(s):  
Vineela Kadiyala ◽  
Catharine L. Smith
Keyword(s):  
Molecular Chaperones ◽  
Hormone Receptors ◽  
Target Genes ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Receptor Signaling ◽  
Receptor Function ◽  
X Receptors ◽  
Lysine Deacetylases

AbstractLysine deacetylases have been known to regulate nuclear receptor function for many years. In the unliganded state, nuclear receptors that form heterodimers with retinoid X receptors, such as the retinoic acid and thyroid hormone receptors, associate with deacetylases to repress target genes. In the case of steroid receptors, binding of an antagonist ligand was initially reported to induce association of deacetylases to prevent activation of target genes. Since then, deacetylases have been shown to have diverse functions in steroid receptor signaling, from regulating interactions with molecular chaperones to facilitating their ability to activate transcription. The purpose of this review is to summarize recent studies on the role of deacetylases in steroid receptor signaling, which show deacetylases to be highly versatile regulators of steroid receptor function.

scholarly journals New Modes of Action for Endocrine-Disrupting Chemicals

2006 ◽  
Vol 20 (3) ◽  
pp. 475-482 ◽  
Author(s):  
Michelle M. Tabb ◽  
Bruce Blumberg
Keyword(s):  
Steroid Hormones ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Methylation Status ◽  
Endocrine Disrupting Chemicals ◽  
Steroid Hormone Receptors ◽  
Protein Kinase Activity ◽  
Naturally Occurring ◽  
Endocrine Disrupting ◽  
Xenobiotic Chemicals

Abstract Endocrine-disrupting chemicals (EDC) are commonly considered to be compounds that mimic or block the transcriptional activation elicited by naturally circulating steroid hormones by binding to steroid hormone receptors. For example, the Food Quality Protection Act of 1996 defines EDC as those, that “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate.” The definition of EDC was later expanded to include those that act on the estrogen, androgen, and thyroid hormone receptors. In this minireview, we discuss new avenues through which xenobiotic chemicals influence these and other hormone-dependent signaling pathways. EDC can increase or block the metabolism of naturally occurring steroid hormones and other xenobiotic chemicals by activating or antagonizing nuclear hormone receptors. EDC affect the transcriptional activity of nuclear receptors by modulating proteasome-mediated degradation of nuclear receptors and their coregulators. Xenobiotics and environmental contaminants can act as hormone sensitizers by inhibiting histone deacetylase activity and stimulating mitogen-activated protein kinase activity. Some endocrine disrupters can have genome-wide effects on DNA methylation status. Others can modulate lipid metabolism and adipogenesis, perhaps contributing to the current epidemic of obesity. Additional elucidation of these new modes of endocrine disruption will be key in understanding the nature of xenobiotic effects on the endocrine system.

scholarly journals Steroid Receptor Coactivator 3 Regulates Synaptic Plasticity and Hippocampus-dependent Memory

2021 ◽  
Author(s):  
Hai-Long Zhang ◽  
Bing Zhao ◽  
Pin Yang ◽  
Yin-Quan Du ◽  
Wei Han ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Steroid Hormones ◽  
Hippocampal Neurons ◽  
Short Term Memory ◽  
Steroid Receptors ◽  
Long Term Potentiation ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator ◽  
Term Potentiation ◽  
And Function

AbstractSteroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) – a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/− mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. We further demonstrated that the deficient learning and memory in Src3+/− mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/− mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.

scholarly journals Extranuclear Steroid Receptors: Nature and Actions

2007 ◽  
Vol 28 (7) ◽  
pp. 726-741 ◽  
Author(s):  
Stephen R. Hammes ◽  
Ellis R. Levin
Keyword(s):  
Steroid Hormones ◽  
Cell Fate ◽  
Cancer Biology ◽  
Steroid Receptors ◽  
Regulation Of Gene Expression ◽  
Steroid Receptor ◽  
Reproductive Organ ◽  
Structural Determinants ◽  
And Function

Rapid effects of steroid hormones result from the actions of specific receptors localized most often to the plasma membrane. Fast-acting membrane-initiated steroid signaling (MISS) 1leads to the modification of existing proteins and cell behaviors. Rapid steroid-triggered signaling through calcium, amine release, and kinase activation also impacts the regulation of gene expression by steroids, sometimes requiring integration with nuclear steroid receptor function. In this and other ways, the integration of all steroid actions in the cell coordinates outcomes such as cell fate, proliferation, differentiation, and migration. The nature of the receptors is of intense interest, and significant data suggest that extranuclear and nuclear steroid receptor pools are the same proteins. Insights regarding the structural determinants for membrane localization and function, as well as the nature of interactions with G proteins and other signaling molecules in confined areas of the membrane, have led to a fuller understanding of how steroid receptors effect rapid actions. Increasingly, the relevance of rapid signaling for the in vivo functions of steroid hormones has been established. Examples include steroid effects on reproductive organ development and function, cardiovascular responsiveness, and cancer biology. However, although great strides have been made, much remains to be understood concerning the integration of extranuclear and nuclear receptor functions to organ biology. In this review, we highlight the significant progress that has been made in these areas.

scholarly journals Review of the in Vivo Functions of the p160 Steroid Receptor Coactivator Family

2003 ◽  
Vol 17 (9) ◽  
pp. 1681-1692 ◽  
Author(s):  
Jianming Xu ◽  
Qingtian Li
Keyword(s):  
Transcription Factors ◽  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Steroid Receptor ◽  
Molecular Structures ◽  
Endocrine Regulation ◽  
Steroid Receptor Coactivator

Abstract The p160 steroid receptor coactivator (SRC) gene family contains three homologous members, which serve as transcriptional coactivators for nuclear receptors and certain other transcription factors. These coactivators interact with ligand-bound nuclear receptors to recruit histone acetyltransferases and methyltransferases to specific enhancer/promotor regions, which facilitates chromatin remodeling, assembly of general transcription factors, and transcription of target genes. This minireview summarizes our current knowledge about the molecular structures, molecular mechanisms, temporal and spatial expression patterns, and biological functions of the SRC family. In particular, this article highlights the roles of SRC-1 (NCoA-1), SRC-2 (GRIP1, TIF2, or NCoA-2) and SRC-3 (p/CIP, RAC3, ACTR, AIB1, or TRAM-1) in development, organ function, endocrine regulation, and nuclear receptor function, which are defined by characterization of the genetically manipulated animal models. Furthermore, this article also reviews our current understanding of the role of SRC-3 in breast cancer and discusses possible mechanisms for functional specificity and redundancy among SRC family members.

scholarly journals Nuclear receptors, their coactivators and modulation of transcription.

1999 ◽  
Vol 46 (1) ◽  
pp. 77-89 ◽  
Author(s):  
M Manteuffel-Cymborowska
Keyword(s):  
Transcription Factors ◽  
Histone Deacetylase ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Target Genes ◽  
Membrane Receptors ◽  
Special Role ◽  
Multicomponent Complex ◽  
Associated Proteins

Nuclear receptors are ligand-dependent transcription factors which can also be activated in the absence of their lipophilic ligands by signaling substances acting on cell membrane receptors. This ligand-independent activation indicates the importance of nuclear receptor phosphorylation for their function. Nuclear receptor-mediated transcription of target genes is further increased by interactions with recruited coactivators forming a novel family of nuclear proteins. CBP/p300, a coactivator of different classes of transcription factors, including the tumor suppressor protein p53, plays a special role acting as a bridging protein between inducible transcription factors and the basal transcription apparatus, and as an integrator of diverse signaling pathways. Coactivators of nuclear receptors and associated proteins forming a multicomponent complex have an intrinsic histone acetylase activity in contrast to nuclear receptor and heterodimer Mad-Max corepressors, which recruit histone deacetylase. Similarly the Rb protein interacts with histone deacetylase to repress transcription of cell cycle regulatory genes. Targeted histone acetylation/deacetylation results in remodeling of chromatin structure and correlates with activation/repression of transcription. Recent data point to the important role of coactivator proteins associated with inducible transcription factors in transcription regulation, and in the integration of multiple signal transduction pathways within the nucleus.

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