The evolution of the nuclear receptor superfamily

Escrivà, Héctor; Bertrand, Stéphanie; Laudet, Vincent

doi:10.1042/bse0400011

Cited by 180 publications

(142 citation statements)

References 55 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…The necessity to design the primers in highly conserved regions in order to clone the rabbit retinoid receptors probably contributed to the high degree of sequence homology with the other species. Nevertheless this strong homology for each RAR and RXR was anticipated by the phylogenic studies of Escriva et al (2004). Similar homology was found in terms of predictive amino acid sequence (96 to 100% for RARs and 93 to 100% for RXRs, data not shown).…”

Section: Discussionsupporting

confidence: 82%

Expression of retinoid receptors during rabbit lung development

Coste

Gallot²,

Marceau³

et al. 2007

Animal

View full text Add to dashboard Cite

Rabbit lung is often used to study the pathophysiology of some congenital anomalies affecting the lung because its development is very comparable with that of human. Retinoids and the molecular transducers of the retinoic signal play a crucial role in mammalian lung development. In the rabbit, the molecular retinoic pathway has so far been poorly studied. As a first step in elucidating this process, we aimed to identify the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We cloned a part of the nuclear receptors (RARs and RXRs), and we used reverse transcription -polymerase chain reaction (RT-PCR) and immunohistochemistry assays to demonstrate the presence of RAR (a,b) and RXR (a, b) at all stages of rabbit lung development. Our results initiate further analysis into the molecular and genetic functions of retinoids during normal and pathological rabbit lung development including the surgical model of congenital diaphragmatic hernia.Keywords: lung development, rabbits, retinoids, retinoic acid receptor, retinoid X receptor IntroductionMany factors including hormonal, biochemical and physical factors have been identified that modulate growth and development of the lung (Keijzer et al., 2000;Cardoso, 2001;Copland and Post, 2004;Rajatapiti et al., 2005). Among the variety of biochemical agents identified so far, retinoids (active derivatives of vitamin A) play a clearly defined role in lung development at its different stages (Gallot et al., 2005;Maden, 2004). Vitamin A (retinol) exerts important effects upon a vast number of development processes via signalling through heterodimerization complexes comprising retinoic acid receptors (RARs) and retinoid X receptors (RXRs) (Chambon, 1996). These receptors belong to the steroid/thyroid hormone receptor super family of ligand-inducible transcription regulators known to control the expression of target genes. All members of this family share a strongly conserved modular structure with discrete functional domains for ligand binding, DNA binding and transactivation. There are three RAR isotypes (RARa, b, g) activated by both all-trans and 9-cis retinoic acid (RA) and three retinoid X receptors (RXRa, b, g) only activated by 9-cis RA (Bastien and Rochette-Egly, 2004).The RAR and RXR proteins interact with each other to form RAR/RXR heterodimers which are able to bind to specific DNA sequences called RA responsive elements usually located within the 5 0 -regulatory region of retinoid-regulated genes.The importance of vitamin A in vertebrate lung development was first demonstrated by the observation that foetuses from pregnant rats which were fed a vitamin Adeficient diet had either agenesis of the left lung or rudimentary lung buds (Warkany and Wilson, 1948;Chazaud et al., 2003). Double mutant mice RARa, b 2/2 revealed defects comparable with the consequences of vitamin A deficiency including hypoplastic lungs (Mendelsohn et al., 1994;Kastner et al., 1997;Mascrez et al., 1998). Abnormalities in the vitamin A status and/or metabolism may also play a role in t...

show abstract

Section: Discussionsupporting

confidence: 82%

Expression of retinoid receptors during rabbit lung development

Coste

Gallot²,

Marceau³

et al. 2007

Animal

View full text Add to dashboard Cite

show abstract

“…Both the endocrine and adopted orphan receptors may have evolved from a phylogenetically ancient transcriptional regulator that underwent multiple duplications and divergences. As a result, the NR superfamily is divided into two broad groups: 1) the transcription factors for which physiologic ligand-dependent activities have been identified; and 2) factors for which physiologic ligands have yet to be identified: the orphan nuclear receptors (Escriva et al 2004). Unlike the endocrine receptors that generally translocate from the cytosol to the nucleus upon ligand binding, the orphan and adopted orphan receptors tend to be constitutively nuclear.…”

Section: Nuclear Hormone Receptorsmentioning

confidence: 99%

Nuclear receptors, mitochondria and lipid metabolism

2008

View full text Add to dashboard Cite

Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function.

show abstract

“…Activation of ER stimulates cell proliferation and is associated with cancer-causing effects through tumor promotion, whereas activation of ER stimulates terminal cell differentiation and may contribute to anticancer effects (Foster et al, 2004). Many xenoestrogens, especially organochlorine pesticides have been shown to disrupt endocrine processes by acting as agonists on ER and/or antagonists on ER (Lemaire et al, 2006) and also possibly as antagonists on androgenic receptors (ARs) (Escriva et al, 2004;Sonnenschein & Soto, 1998). Indeed, in addition to the induction of a more or less agonistic effects by interacting with ER , many pesticides used such as chlordecone, endosulfan, aldrin, dieldrin and endrin have been shown to be associated with antagonistic effects by activating ER , meaning that agonistic effects involving ER in addition to antagonistic effects involving ER may strongly contribute to the tumor promoting effects of these pesticides (Lemaire et al, 2006).…”

Section: Pesticides As Tumor Promotersmentioning

confidence: 99%