scholarly journals Hormone Control Regions mediate opposing steroid receptor-dependent genome organizations

2017 ◽  
Author(s):  
François Le Dily ◽  
Enrique Vidal ◽  
Yasmina Cuartero ◽  
Javier Quilez ◽  
Silvina Nacht ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
List Type ◽  
Transcriptional Responses ◽  
Long Distance ◽  
Topologically Associating Domains ◽  
Hormone Control ◽  
Hormone Signals ◽  
Control Regions

AbstractIn breast cancer cells, topologically associating domains (TADs) behave as units of hormonal gene regulation with transcripts within hormone responsive TADs changing coordinately their expression in response to steroid hormones. Here we further described that responsive TADs contain 20-100 kb-long clusters of intermingled estrogen receptor (ER) and progesterone receptor (PR) binding sites, hereafter called Hormone-Control Regions (HCRs). We identified more than 200 HCRs, which are frequently bound by ER and PR even in the absence of hormones. These HCRs establish steady long-distance inter-TAD interactions between them and organize characteristic looping structures with promoters even in the absence of hormones. This organization is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms integrating different signals resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest that steroid hormone receptors act not only as hormone-regulated sequence-specific transcription factors, but also as local and global genome organizers.HighlightsHormone responsive TADs are organized around conserved large regulatory regions (HCRs) enriched in ER and PR.HCR contact promoters within their TADs and engaged long-range inter-TADs contacts between them.Binding of the receptors in absence of hormones maintains global HCR-HCR interactions and intra-TADs regulatory loops.HCRs can integrate the hormone signals in divergent ways leading to opposite restructuration of TADs in response to Estrogens or Progestins.

scholarly journals Steroid hormone receptors and direct effects of steroid hormones on ram spermatozoa

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. 469-481 ◽  
Author(s):  
S Gimeno-Martos ◽  
M González-Arto ◽  
A Casao ◽  
M Gallego ◽  
J A Cebrián-Pérez ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Steroid Hormones ◽  
Acrosome Reaction ◽  
Hormone Receptors ◽  
Female Genital Tract ◽  
Equatorial Region ◽  
Steroid Hormone Receptors ◽  
Apical Region ◽  
Ram Sperm

This study was based on the assumption that steroid hormones present in the female genital tract may have a rapid effect on ram spermatozoa by interaction with specific surface receptors. We demonstrate the presence of progesterone (PR) and estrogen (ER) receptors in ram spermatozoa, their localization changes duringin vitrocapacitation and the actions of progesterone (P4) and 17β-estradiol (E2) on ram sperm functionality. Immunolocalization assays revealed the presence of PR mainly at the equatorial region of ram spermatozoa. Western blot analyses showed three bands in ram sperm protein extracts of 40–45 kDa, compatible with those reported for PR in the human sperm membrane, and both classical estrogen receptors (66 kDa, ERα and 55 kDa, ERβ). ERα was located in the postacrosomal region of all the spermatozoa and ERβ on the apical region of 63.7% of the cells. The presence of ERβ was correlated with the percentage of non-capacitated spermatozoa evaluated by chlortetracycline staining (R = 0.848,P < 0.001). This significantly decreased afterin vitrocapacitation and nearly disappeared when acrosome reaction was induced. The addition of P4 and E2 beforein vitrocapacitation resulted in a higher (P < 0.001) acrosome-reacted sperm rate compared with the control (13.0%), noticeably greater after 3 h and when added to a high-cAMP medium (37.3% and 47.0% with E2 and P4, respectively). In conclusion, the results of this study demonstrate for the first time that ovine spermatozoa have progesterone and estrogen receptors and that both steroid hormones are related with the induction of the acrosome reaction.

scholarly journals 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Coregulators as mediators of mineralocorticoid receptor signalling diversity

2017 ◽  
Vol 234 (1) ◽  
pp. T23-T34 ◽  
Author(s):  
Peter J Fuller ◽  
Jun Yang ◽  
Morag J Young
Keyword(s):  
Protein Interactions ◽  
Mineralocorticoid Receptor ◽  
Hormone Receptors ◽  
Target Genes ◽  
Steroid Hormone Receptors ◽  
Protein Protein Interactions ◽  
Transcriptional Responses ◽  
Functional Roles ◽  
Regulatory Processes ◽  
Coregulatory Proteins

The cloning of the mineralocorticoid receptor (MR) 30 years ago was the start of a new era of research into the regulatory processes of MR signalling at target genes in the distal nephron, and subsequently in many other tissues. Nuclear receptor (NR) signalling is modified by interactions with coregulatory proteins that serve to enhance or inhibit the gene transcriptional responses. Over 400 coregulatory proteins have been described for the NR super family, many with functional roles in signalling, cellular function, physiology and pathophysiology. Relatively few coregulators have however been described for the MR although recent studies have demonstrated both ligand and/or tissue selectivity for MR-coregulator interactions. A full understanding of the cell, ligand and promoter-specific requirements for MR-coregulator signalling is an essential first step towards the design of small molecular inhibitors of these protein-protein interactions. Tissue-selective steroidal or non-steroidal modulators of the MR are also a desired therapeutic goal. Selectivity, as for other steroid hormone receptors, will probably depend on differential expression and recruitment of coregulatory proteins.

scholarly journals Differential Responses to Steroid Hormones in Fibroblasts From the Vocal Fold, Trachea, and Esophagus

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1000-1009 ◽  
Author(s):  
Shigeyuki Mukudai ◽  
Ken Ichi Matsuda ◽  
Takeshi Nishio ◽  
Yoichiro Sugiyama ◽  
Hideki Bando ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Steroid Hormones ◽  
Vocal Fold ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Vocal Folds ◽  
Steroid Hormone Receptors ◽  
Male Rats ◽  
Target Cells ◽  
Cultured Fibroblasts

Abstract There is accumulating evidence that fibroblasts are target cells for steroids such as sex hormones and corticoids. The characteristics of fibroblasts vary among tissues and organs. Our aim in this study is to examine differences in responses to steroid hormones among fibroblasts from different cervicothoracic regions. We compared the actions of steroid hormones on cultured fibroblasts from the vocal folds, which are considered to be the primary target of steroid hormones, and the trachea and esophagus in adult male rats. Expression of steroid hormone receptors (androgen receptor, estrogen receptor α, and glucocorticoid receptor) was identified by immunofluorescence histochemistry. Androgen receptor was much more frequently expressed in fibroblasts from the vocal fold than in those from the trachea and esophagus. Cell proliferation analysis showed that administration of testosterone, estradiol, or corticosterone suppressed growth of all 3 types of fibroblasts. However, mRNA expression for extracellular matrix–associated genes, including procollagen I and III and elastin, and hyaluronic acid synthase I was elevated only by addition of testosterone to fibroblasts from the vocal fold. These results indicate that each steroid hormone exerts region-specific effects on cervicothoracic fibroblasts with different properties through binding to specific receptors.

Characteristics of steroid hormone receptors in cultured MC3T3-E1 osteoblastic cells and effect of steroid hormones on cell proliferation

1992 ◽  
Vol 51 (5) ◽  
pp. 376-381 ◽  
Author(s):  
Akihiro Masuyama ◽  
Yasuyoshi Ouchi ◽  
Fumiyasu Sato ◽  
Takyauki Hosoi ◽  
Tetsuro Nakamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Steroid Hormones ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Osteoblastic Cells

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 Historical Perspectives: An abridged history of sex steroid hormone receptor action

2001 ◽  
Vol 91 (4) ◽  
pp. 1854-1859 ◽  
Author(s):  
Stacey A. Fannon ◽  
Regina M. Vidaver ◽  
Sherry A. Marts
Keyword(s):  
Human Health ◽  
Steroid Hormones ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Future Research ◽  
Steroid Hormone Receptor ◽  
Historical Perspectives ◽  
Receptor Action

The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report Exploring the Biological Contributions to Human Health: Does Sex Matter?, the effects of steroid hormones and defects in steroid hormone receptor action have a profound impact on human health and disease. Future research directives include the development of potent, selective steroid receptor modulators, the elucidation of nongenomic steroid hormone effects, and further exploration of hormone-genome interactions.

scholarly journals Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPK

2003 ◽  
Vol 12 (6) ◽  
pp. 329-337 ◽  
Author(s):  
M. Castro-caldas ◽  
A. F. Mendes ◽  
C. B. Duarte ◽  
M. C. F. Lopes
Keyword(s):  
Steroid Hormones ◽  
P38 Mapk ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Annexin 1 ◽  
Creb Activation ◽  
Anti Inflammatory

Aims:Annexin 1 (ANXA1), a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex), and the estrogen hormone, 17β-estradiol (E2β), induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP-responsive element (CRE). In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins (CREB) in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen-activated protein kinase (MAPK).Results:The results show that Dex and E2β were as effective as the cAMP analogue, dBcAMP, in inducing CREB activation. On the other hand, dBcAMP induced ANXA1 synthesis as effectively as these steroid hormones. Furthermore, the cAMP antagonist, Rp-8-Br-cAMPS, and the specific p38 MAPK inhibitor, SB203580, effectively prevented Dex-induced, E2β-induced and dBcAMP-induced CREB activation and ANXA1 synthesis.Conclusions:Taken together, our results suggest that, in CCRF-CEM cells, Dex-induced and E2β-induced ANXA1 expression requires the activation of the transcription factor CREB, which in turn seems to be mediated by cAMP and the p38 MAPK. These findings also suggest that, besides the nuclear steroid hormone receptors, other transcription factors, namely CREB, may play important roles in mediating the anti-inflammatory actions of glucocorticoids and oestrogen hormones.

scholarly journals Non-genomic actions of sex steroid hormones

2003 ◽  
Vol 148 (3) ◽  
pp. 281-292 ◽  
Author(s):  
T Simoncini ◽  
AR Genazzani
Keyword(s):  
Cell Membrane ◽  
Steroid Hormones ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Steroid Hormone ◽  
Regulation Of Gene Expression ◽  
Steroid Hormone Receptors ◽  
Target Cells ◽  
Specific Response ◽  
Receptor Modulation

Steroid hormone receptors have been traditionally considered to act via the regulation of transcriptional processes, involving nuclear translocation and binding to specific response elements, and ultimately leading to regulation of gene expression. However, novel non-transcriptional mechanisms of signal transduction through steroid hormone receptors have been identified. These so-called 'non-genomic' effects do not depend on gene transcription or protein synthesis and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Several relevant biological actions of steroids have been associated with this kind of signaling. Ubiquitous regulatory cascades such as mitogen-activated protein kinases, the phosphatidylinositol 3-OH kinase and tyrosine kinases are modulated through non-transcriptional mechanisms by steroid hormones. Furthermore, steroid hormone receptor modulation of cell membrane-associated molecules such as ion channels and G-protein-coupled receptors has been shown. TIssues traditionally considered as 'non-targets' for classical steroid actions are instead found to be vividly regulated by non-genomic mechanisms. To this aim, the cardiovascular and the central nervous system provide excellent examples, where steroid hormones induce rapid vasodilatation and neuronal survival via non-genomic mechanisms, leading to relevant pathophysiological consequences. The evidence collected in the past Years indicates that target cells and organs are regulated by a complex interplay of genomic and non-genomic signaling mechanisms of steroid hormones, and the integrated action of these machineries has important functional roles in a variety of pathophysiological processes. The understanding of the molecular basis of the rapid effects of steroids is therefore important, and may in the future turn out to be of relevance for clinical purposes.

scholarly journals The Octopus vulgaris Estrogen Receptor Is a Constitutive Transcriptional Activator: Evolutionary and Functional Implications

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3861-3869 ◽  
Author(s):  
June Keay ◽  
Jamie T. Bridgham ◽  
Joseph W. Thornton
Keyword(s):  
Estrogen Receptor ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Functional Characterization ◽  
Transcriptional Activator ◽  
Steroid Hormone Receptors ◽  
Octopus Vulgaris ◽  
Estrogen Response ◽  
Estrogen Response Elements

Steroid hormones such as estrogens and androgens are important regulators of reproduction, physiology, and development in a variety of animal taxa, including vertebrates and mollusks. Steroid hormone receptors, which mediate the classic cellular responses to these hormones, were thought to be vertebrate specific, which left the molecular mechanisms of steroid action in invertebrates unresolved. Recently an estrogen receptor (ER) ortholog was isolated from the sea hare Aplysia californica, but the functional significance of the receptor was unclear because estrogens and other steroids are not known to be important in that species. Furthermore, the Aplysia ER was found to be a constitutive transcriptional activator, but it was unclear whether the estrogen independence of the ER was an Aplysia-specific novelty or a more ancient character general to the mollusks. Here we report on the isolation and functional characterization of the first ER ortholog from an invertebrate in which estrogens are produced and play an apparent role, the cephalopod Octopus vulgaris. We show that the Octopus ER is a strong constitutive transcriptional activator from canonical estrogen response elements. The receptor does not bind estradiol and is unresponsive to estrogens and other vertebrate steroid hormones. These characteristics are similar to those observed with the Aplysia ER and support the hypothesis that the evolving ER gained constitutive activity deep in the mollusk lineage. The apparent reproductive role of estrogens in Octopus and other mollusks is unlikely to be mediated by the ER and may take place through an ancient, non-ER-mediated pathway.

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