Retinoids gene expression

Horiguchi, T., Nishikawa, T., and Ohta, Y. et al. (2007). Retinoid X receptor gene expression and protein content in tissues of the rock sheU Thais clavigera. Aquatic Toxicology 84, 379-388. 

Sizemore N, Kasturi L, Gorodeski G, Eckert RL, Jetten AM, and Rorke EA [1993] Retinoid regulation of human ectocervical epithelial cell transglutaminase activity and keratin gene expression. Differentiation 54 219-225... 

Nuclear hormone receptors, including those for the principal classes of steroids, retinoids, vitamin D, and thyroid hormones, are transcription factors that influence gene expression. 

McGowan, S. E., Doro, M. M., and Jackson, S. (1997). Endogenous retinoids increase perinatal elastin gene expression in rat lung fibroblasts and fetal explants. Am. J. Physiol. 273, L410-L416. 

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

Like other retinoids, tazarotene (Razorac) acts by binding to RARs and altering gene expression. Tazarotene appears to be particularly selective for the retinoid receptors RAR-(3 and RAR-y,but the clinical significance of this observation is unknown. 

It is an acetylenic retinoid prodrug which is hydrolysed to active metabolite tazarotenic acid, binds to retinoic acid receptors resulting in modified gene expression. 

A further, more dramatic difference to the steroid hormone receptors is the localization of the receptors. The receptors for the retinoids (RAR and RXR, see table 4.1), the T3 hormone (T3R) and vitamin D3 (VDR) are mainly localized in the nucleus and their activity is not controlled by the heat shock proteins. The receptors also bind the corresponding HRE in the absence of hormone, in which case they can then act as repressors of gene activity. In the presence of the hormone an activation of gene expression is usually observed. 

Retinoids also modulate gene expression acting and the post-transcriptional level. The P-carotene has also important implications from the clinical point of view. All E retinoic acid is used for patients with acute promyelocytic leukemia [1],... 

The large group of steroid, retinoic acid (retinoid), and thyroid hormones exert at least part of their effects by a mechanism fundamentally different from that of other hormones they act in the nucleus to alter gene expression. We therefore discuss their mode of action in detail in Chapter 28, along with other mechanisms for regulating gene expression. Here we give a brief overview. 

FIGURE 12-40 General mechanism by which steroid and thyroid hormones, retinoids, and vitamin D regulate gene expression. The details of transcription and protein synthesis are discussed in Chapters 26 and 27. At least some steroids also act through plasma membrane receptors by a completely different mechanism. 

Steroid, vitamin D, retinoid, and thyroid hormones enter target cells and alter gene expression by interacting with specific nuclear receptors. 

Freebern, W.J., Osman, A., Niles, E.G., Christen, L. and LoVerde, P.T. (1999a) Identification of a cDNA encoding a retinoid X receptor homologue from Schistosoma mansoni. Evidence for a role in female-specific gene expression, journal of Biological Chemistry 274, 4577 t585. 

Tazarotene (Tazorac) is an acetylenic retinoid prodrug that is hydrolyzed to its active form by an esterase. The active metabolite, tazarotenic acid, binds to retinoic acid receptors, resulting in modified gene expression. The precise mechanism of action in psoriasis is unknown but may relate to both anti-inflammatory and antiproliferative actions. Tazarotene is absorbed percutaneously, and teratogenic systemic concentrations may be achieved if applied to more than 20% of total body surface area. Women of childbearing potential must therefore be advised of the risk prior to initiating therapy, and adequate birth control measures must be utilized while on therapy. 

The form of vitamin A that is needed for regulating vitamin A-dependent gene expression is retinoic acid.All-fraws-retinoic acid can interact with each of the three RARs (RARa, RAR(3, and RARy) and each of the three RXRs (RXRa, RXR(3, and RXRy). 9-cX-Retinoic acid binds and effectively transactivates only the RXRs. The RARs and the RXRs recognize well-defined exacting response elements, termed retinoic acid response elements (RAREs) and retinoid X response elements (RXREs) that are present in the promoter regions of responsive genes. The RARs and RXRs bind to RAREs and/or RXREs as dimers, either homodimers or heterodimers. 

Ethier, I., Beaudry, G., St-Hilaire, M., Milbrandt, J., Roulliard, C., Levesque, D. (2004). The transcription factor NGFI-B (Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal neuropeptide gene expression. Neuropsychopharmacology, 29, 335-346. 

An example of gene expression can be illustrated by consideration of the action of steroid hormones, and in the control of sterol biosynthesis. Steroid hormones enter the cell by diffusion through the plasma membrane and bind to their steroid hormone receptor. These receptors are part of a large related family that includes those for glucocorticoids, oestrogens, androgens, thyroid hormone, calcitriol and the retinoids. All steroid hormone receptors are zinc finger transcription factors. The receptor must ... 

Retinoic acid modulates gene expression and tissue differentiation, acting by way of nuclear receptors. Historically, there was confusion between the effects of deficiency of vitamins A and D by the 1950s, it was believed that the confusion had been resolved. Elucidation of the nuclear actions of the two vitamins has shown that, in many systems, the two act in concert, forming retinoid-vitamin D heterodimeric receptors hypervitaminosis A can antagonize the actions of vitamin D. 

Villarroya F, Giralt M, and Iglesias R (1999) Retinoids and adipose tissues metabolism, cell differentiation and gene expression. International Journal of Obesity and Related Metabolic Disorders 23,1-6. 

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