On the Sterols of Some Ascidians

Voogt, P.A.; Rheenen, J.W.A. van

doi:10.3109/13813457509071400

Cited by 20 publications

(6 citation statements)

References 5 publications

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“…There have been few detailed studies of steroidal compounds in C. intestinalis. One study reported that the major sterols of adult C. intestinalis were cholest-5-en-3β-ol (68.7%), 24-methylcholest-5-en-3β-ol (7.3%), 24-ethyl-cholesta-5,22-dien-3β-ol (6.3%), and 24-methylcholesta-5,22-dien-3β-ol (5.3%); thirty carbon sterols found in some other invertebrates were not detected [40]. Another study found dehydroepiandrosterone, cortisone, and cortisol in testes, and cortisone in C. intestinalis ovary.…”

Section: Discussionmentioning

confidence: 99%

Ligand specificity and evolution of liver X receptors

Reschly

Ni²,

Welsh³

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

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Liver X receptors (LXRs) are key regulators of lipid and cholesterol metabolism in mammals. Little is known, however, about the function and evolution of LXRs in non-mammalian species. The present study reports the cloning of LXRs from African clawed frog (Xenopus laevis), Western clawed frog (Xenopus tropicalis), and zebrafish (Danio rerio), and their functional characterization and comparison with human and mouse LXRs. Additionally, an ortholog of LXR in the chordate invertebrate Ciona intestinalis was cloned and functionally characterized. Ligand specificities of the frog and zebrafish LXRs were very similar to LXRα and LXRβ from human and mouse. All vertebrate LXRs studied were activated robustly by the synthetic ligands T-0901317 and GW3965 and by a variety of oxysterols. In contrast, Ciona LXR was not activated by T-0901317 or GW3965 but was activated by a limited number of oxysterols, as well as some androstane and pregnane steroids. Pharmacophore analysis, homology modeling, and docking studies of Ciona LXR predict a receptor with a more restricted ligand-binding pocket and less intrinsic disorder in the ligand-binding domain compared to vertebrate LXRs. The results suggest that LXRs have a long evolutionary history, with vertebrate LXRs diverging from invertebrate LXRs in ligand specificity.

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Section: Discussionmentioning

confidence: 99%

Ligand specificity and evolution of liver X receptors

Reschly

Ni²,

Welsh³

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

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“…There are no clear correlates of vitamin D or bile salts yet described in invertebrates, and as a result, endogenous ligands for the ciVDR/PXR would likely be different from those for vertebrate VDRs and PXRs. Ciona intestinalis is, however, capable of synthesizing steroid hormones and also accumulates cholesterol and other sterols from dietary sources [ 72 , 73 ]. The endogenous activators of the ciVDR/PXR may be as yet undescribed steroidal molecules that have structural similarity to vertebrate vitamins and/or bile salts.…”

Section: Discussionmentioning

confidence: 99%

Functional evolution of the vitamin D and pregnane X receptors

et al. 2007

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Background: The vitamin D receptor (VDR) and pregnane X receptor (PXR) are nuclear hormone receptors of the NR1I subfamily that show contrasting patterns of cross-species variation. VDR and PXR are thought to have arisen from duplication of an ancestral gene, evident now as a single gene in the genome of the chordate invertebrate Ciona intestinalis (sea squirt). VDR genes have been detected in a wide range of vertebrates including jawless fish. To date, PXR genes have not been found in cartilaginous fish. In this study, the ligand selectivities of VDRs were compared in detail across a range of vertebrate species and compared with those of the Ciona VDR/PXR. In addition, several assays were used to search for evidence of PXR-mediated hepatic effects in three model non-mammalian species: sea lamprey (Petromyzon marinus), zebrafish (Danio rerio), and African clawed frog (Xenopus laevis).

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“…Given that there are no clear correlates of vitamin D or bile salts yet described in invertebrates, endogenous ligands for the Ciona VDR/PXR/CAR would logically be different from those for vertebrate VDRs and PXRs. Ciona intestinalis is, however, capable of synthesizing steroid hormones and also accumulates cholesterol and other sterols from dietary sources (Delrio et al, 1971; Voogt and van Rheenan, 1975). The endogenous activators of the Ciona VDR/PXR/CAR may be as yet undescribed molecules that have structural similarity to vertebrate vitamins and/or bile salts or they may be structurally unique but sharing a similar three-dimensional pharmacophore to ligands for the vertebrate receptors.…”

Section: The Co-evolution Of Biochemical Pathways and Nr1h And Nr1mentioning

confidence: 99%

Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR

Krasowski

Ni²,

Hagey

et al. 2011

Molecular and Cellular Endocrinology

103

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Nuclear hormone receptors (NHRs) are transcription factors that work in concert with co-activators and co-repressors to regulate gene expression. Some examples of ligands for NHRs include endogenous compounds such as bile acids, retinoids, steroid hormones, thyroid hormone, and vitamin D. This review describes the evolution of liver X receptors α and β (NR1H3 and 1H2, respectively), farnesoid X receptor (NR1H4), vitamin D receptor (NR1I1), pregnane X receptor (NR1I2), and constitutive androstane receptor (NR1I3). These NHRs participate in complex, overlapping transcriptional regulation networks involving cholesterol homeostasis and energy metabolism. Some of these receptors, particularly PXR and CAR, are promiscuous with respect to the structurally wide range of ligands that act as agonists. A combination of functional and computational analyses has shed light on the evolutionary changes of NR1H and NR1I receptors across vertebrates, and how these receptors may have diverged from ancestral receptors that first appeared in invertebrates.

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On the Sterols of Some Ascidians

Cited by 20 publications

References 5 publications

Ligand specificity and evolution of liver X receptors

Ligand specificity and evolution of liver X receptors

Functional evolution of the vitamin D and pregnane X receptors

Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR

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