Nuclear Receptors in Pregnancy and Outcomes: Clinical Perspective
Adv Exp Med Biol. 2022;1390:3-19. doi: 10.1007/978-3-031-11836-4_1.ABSTRACTPregnancy is characterised by profound hormonal and metabolic changes in the mother. Both oestrogen and progesterone, along with their respective nuclear receptors, have an important role in maintaining a healthy pregnancy. Equally, other nuclear receptors such as LXR, FXR and the PPARs play important roles in the gradual alterations in metabolism that ensure survival of mother and fetus. Disruptions in nuclear receptor signalling can result in pregnancy disorders such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, hyperten...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Luiza Borges Manna Catherine Williamson Source Type: research

Female Reproductive Systems: Hormone Dependence and Receptor Expression
Adv Exp Med Biol. 2022;1390:21-39. doi: 10.1007/978-3-031-11836-4_2.ABSTRACTThe female reproductive system which consists of the ovaries, uterus (myometrium, endometrium), Fallopian tubes, cervix and vagina is exquisitely sensitive to the actions of steroid hormones. The ovaries play a key role in the synthesis of bioactive steroids (oestrogens, androgens, progestins) that act both within the tissue (intracrine/paracrine) as well as on other reproductive organs following release into the blood stream (endocrine action). Sex steroid receptors encoded by the oestrogen (ESR1, ESR2), progesterone (PR) and androgen (AR) recepto...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Kevin K W Kuan Philippa T K Saunders Source Type: research

Nuclear Receptors in Ovarian Function
Adv Exp Med Biol. 2022;1390:41-58. doi: 10.1007/978-3-031-11836-4_3.ABSTRACTThe ovary undergoes cycles of hormone production that regulate physiological changes necessary for folliculogenesis, ovulation and luteinisation, ultimately contributing to female reproductive success. Crucial to these biological processes is stage-specific nuclear receptor signalling. While the transcriptional regulatory roles of steroid receptors in female fertility and especially ovarian functions have long been documented, non-steroid receptors also play an important part in regulating gene expression at various stages of ovarian development. T...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Doan Thao Dinh Darryl Lyndon Russell Source Type: research

Nuclear Receptors in Energy Metabolism
Adv Exp Med Biol. 2022;1390:61-82. doi: 10.1007/978-3-031-11836-4_4.ABSTRACTNuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical resea...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Alina A Walth-Hummel Stephan Herzig Maria Rohm Source Type: research

Nuclear Receptors and Lipid Sensing
Adv Exp Med Biol. 2022;1390:83-105. doi: 10.1007/978-3-031-11836-4_5.ABSTRACTFluctuations in concentration of diverse lipid classes occur in response to diet and metabolism. These changes are managed and mediated by a cell network of enzymes, pumps, and carriers under the control of the lipid responsive nuclear receptors. The understanding of how dysregulation of lipid metabolism are causes and indicators of disease beyond the cardiovascular system has developed in the last decade. A particular emphasis on the role of lipids and lipid-sensing nuclear receptors has emerged in the fields of cancer and the immune system's int...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: James L Thorne Giorgia Cioccoloni Source Type: research

Corticosteroid Receptors in Cardiac Health and Disease
Adv Exp Med Biol. 2022;1390:109-122. doi: 10.1007/978-3-031-11836-4_6.ABSTRACTNuclear receptors play a central role in both energy metabolism and cardiomyocyte death and survival in the heart. Recent evidence suggests they may also influence cardiomyocyte endowment. Although several members of the nuclear receptor family play key roles in heart maturation (including thyroid hormone receptors) and cardiac metabolism, here, the focus will be on the corticosteroid receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). The heart is an important target for the actions of corticosteroids, yet the homeos...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Jessica R Ivy Gillian A Gray Megan C Holmes Martin A Denvir Karen E Chapman Source Type: research

Physiological Convergence and Antagonism Between GR and PPAR γ in Inflammation and Metabolism
Adv Exp Med Biol. 2022;1390:123-141. doi: 10.1007/978-3-031-11836-4_7.ABSTRACTNuclear receptors (NRs) are transcription factors that modulate gene expression in a ligand-dependent manner. The ubiquitously expressed glucocorticoid receptor (GR) and peroxisome proliferator-activated receptor gamma (PPARγ) represent steroid (type I) and non-steroid (type II) classes of NRs, respectively. The diverse transcriptional and physiological outcomes of their activation are highly tissue-specific. For example, in subsets of immune cells, such as macrophages, the signaling of GR and PPARγ converges to elicit an anti-inflammatory phen...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Marija Dacic Gayathri Shibu Inez Rogatsky Source Type: research

Circadian Rhythm and Nuclear Receptors
Adv Exp Med Biol. 2022;1390:143-153. doi: 10.1007/978-3-031-11836-4_8.ABSTRACTAll life of Earth has evolved mechanisms to track time. This permits anticipation of predictable changes in light/dark, and in most cases also directs fed/fasted cycles, and sleep/wake. The nuclear receptors enjoy a close relationship with the molecular machinery of the clock. Some play a core role within the circadian machinery, other respond to ligands which oscillate in concentration, and physical cross-talk between clock transcription factors, eg cryptochromes, and multiple nuclear receptors also enable coupling of nuclear receptor function t...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: David W Ray Source Type: research

Vitamin D and Gut Health
Adv Exp Med Biol. 2022;1390:155-167. doi: 10.1007/978-3-031-11836-4_9.ABSTRACTVitamin D is a conditionally required nutrient that can either be obtained from skin synthesis following UVB exposure from the diet. Once in the body, it is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D), that regulates gene expression in target tissues by interacting with a ligand-activated transcription factor, the vitamin D receptor (VDR). The first, and most responsive, vitamin D target tissue is the intestine. The classical intestinal role for vitamin D is the control of calcium metabolism through the regu...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: James C Fleet Source Type: research

Estrogen Receptor Alpha and ESR1 Mutations in Breast Cancer
Adv Exp Med Biol. 2022;1390:171-194. doi: 10.1007/978-3-031-11836-4_10.ABSTRACTThe estrogen receptor alpha (ERα) is a nuclear transcription factor that is expressed in more than 70% of all breast cancers. Key genes involved in proliferation and tumor progression are transcriptionally regulated by ERα making it an important therapeutic target. Indeed, the first class of targeted treatments in cancer are endocrine treatments that target ERα either by competitive inhibition, reduced ligand production or receptor degradation. Despite the efficacy of these drugs, resistance to endocrine treatment remains a key clinical chall...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Jaymin M Patel Rinath M Jeselsohn Source Type: research

AR Structural Variants and Prostate Cancer
Adv Exp Med Biol. 2022;1390:195-211. doi: 10.1007/978-3-031-11836-4_11.ABSTRACTTherapeutic interventions for advanced castration-resistant prostate cancer (CRPC) are focused on inhibiting the androgen receptor (AR) through targeting of its C-terminal ligand binding domain (LBD). However, a significant subset of CRPC patients demonstrate primary resistance to androgen deprivation and anti-androgen therapies, suggesting that other targets, outside of the AR, might be pertinent to the cancer progression. One explanation is the expression of androgen receptor splice variants (AR-Vs). So far, more than 20 AR-Vs have been identi...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Laura Cato Maysoun Shomali Source Type: research

ER β and Inflammation
Adv Exp Med Biol. 2022;1390:213-225. doi: 10.1007/978-3-031-11836-4_12.ABSTRACTEstrogen, through the regulation of cytokine production, can act both as pro-inflammatory and anti-inflammatory signals dependent on the tissue context. In breast cancer cells, ERα is known to modulate inflammatory signaling through interaction with NFκB. Whether ERβ has a role in inflammation is less explored. Low levels of ERβ have been corroborated in several immune-related organs and, for example, in colonic epithelial cells. Specifically, an impact of ERβ on colitis and colitis-associated colorectal cancer (CRC) is experimentally suppo...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Linnea Hases Amena Archer Cecilia Williams Source Type: research

Genomic Insights into Non-steroidal Nuclear Receptors in Prostate and Breast Cancer
Adv Exp Med Biol. 2022;1390:227-239. doi: 10.1007/978-3-031-11836-4_13.ABSTRACTAlterations in transcriptional programs are a fundamental feature of prostate (PCa) and breast cancer (BrCa), and frequently target the actions of the principal steroidal nuclear receptors (NRs), namely the androgen receptor (AR) and the estrogen receptor alpha (ERα), respectively. Indeed, the functions of AR and ERα are central to both prostate and mammary gland biology. The genomic interactions of these NRs become highly distorted in part by changing how they functionally interact with a cohort of non-steroidal Type II NRs, which are by cont...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Sajad A Wani Moray J Campbell Source Type: research

Protein Condensation in the Nuclear Receptor Family; Implications for Transcriptional Output
Adv Exp Med Biol. 2022;1390:243-253. doi: 10.1007/978-3-031-11836-4_14.ABSTRACTThe nuclear receptor superfamily is a group of transcriptional regulators that orchestrate multiple vital processes such as inflammation, metabolism, and cell proliferation. In recent years, it has become clear that some nuclear receptors form condensates in living cells. These condensates contain high concentrations of proteins and can contain millions of molecules. At these sites, high concentrations of nuclear receptors and co-factors potentially contribute to efficient transcription. While condensate formation has been observed for some nucl...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Monique D Appelman Elle E Hollaar Jurian Schuijers Saskia W C van Mil Source Type: research

Prostate Cancer Epigenetic Plasticity and Enhancer Heterogeneity: Molecular Causes, Consequences and Clinical Implications
Adv Exp Med Biol. 2022;1390:255-275. doi: 10.1007/978-3-031-11836-4_15.ABSTRACTProstate cancer (PCa) proliferation is dictated by androgen receptor (AR) signaling, which regulates gene expression through cis-regulatory regions including proximal and distal enhancers. The repertoire of AR interactions at enhancers is dependent on tissue and cellular contexts and thus shape a spectrum of phenotypes through such epigenetic heterogeneity. Moreover, PCa is a multifocal disease and displays a high degree of intra- and inter-tumor heterogeneity, adding to the phenotypic complexity. It is increasingly becoming clear that PCa may b...
Source: Advances in Experimental Medicine and Biology - September 15, 2022 Category: Research Authors: Jeroen Kneppers Andries M Bergman Wilbert Zwart Source Type: research