Retinoids General

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

In general, retinoids are also well tolerated in darker skin types however, retinoid dermatitis may cause post-inflammatory hyperpigmentation. In addition, progressive hyperpigmenta-... 

By selectively affecting gene transcription and the consequent production of appropriate target mRNAs, the amounts of specific proteins are changed and metabolic processes are influenced. The influence of each of these hormones is quite specific generally, the hormone affects less than 1% of the genes, mRNA, or proteins in a target cell sometimes only a few are affected. The nuclear actions of steroid, thyroid, and retinoid hormones are quite well defined. Most evidence sug-... 

RH above can represent a very wide variety of xenobi-otics, including drugs, carcinogens, pesticides, petroleum products, and pollutants (such as a mixture of PCBs). In addition, endogenous compounds, such as certain steroids, eicosanoids, fatty acids, and retinoids, are also substrates. The substrates are generally lipophilic and are rendered more hydrophilic by hydroxy-lation. 

The topical retinoid selected should be used once daily at bedtime, beginning with a low-potency formulation. Increased strengths are then initiated according to treatment results and tolerance. Patients should be advised that a worsening of acne symptoms generally occurs in the first few weeks of therapy, with lesion improvement occurring in 3 to 4 months.16 The use of topical retinoids should be avoided in children less than 12 years old and in pregnant women.14... 

Another general method for the preparation of 19,19,19- and 20,20,20-trifluor-oretinals involves the aldol condensation of trifluoroacetone with an ethylenic aldehyde. When performed in the presence of acetic acid and piperidine, it affords an a, S-unsaturated ketone. Applied to cyclocitral and its homologues, the method leads to polyenic trifluoromethyl ketones. From these ketones, the various tri-fluorinated retinoids are prepared by known methods (Figure 4.24). ... 

Vitamin A (retinol, 6.1) is the parent of a range of compounds known as retinoids, which possess the biological activity of vitamin A. In general, animal foods provide preformed vitamin A as retinyl esters (e.g. 6.5, which are easily hydrolysed in the gastrointestinal tract) while plant foods provide precursors of vitamin A, i.e. carotenoids. Only carotenoids with a /3-ionone ring (e.g. /1-carotene) can serve as vitamin A precursors. /3-Carotene (6.6)... 

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. 

Eukaryote organisms primarily respond to external signals by an initial signal perception by receptors. In general, such receptors can be either cytosolic or located on the plasma membrane [13-15]. The former mechanism applies to thyroid hormones (triiodothyronine and tetraiodothyronine or thyroxine), retinoids (e.g. retinoic acid), the insect developmental hormones such as ecdysone, steroid hormones (such as... 

Vitamin A active in the visual process further complicates the matter. The general occurrence of these types of Vitamin A were presented in Section 1.2.1. Most marine based animals (including most terrestrial mammals) rely upon Vitamin A form all their retinoid needs. Freshwater fish generally rely upon Vitamin A2 for their needs and certain orders within Arthropoda rely upon Vitamin A3. 

Writing contemporaneously, Wolf De Luca said42 There is now, we believe, general agreement that vitamin A is to be regarded as a hormone rather than a vitamin in the classical sense of a conenzyme. By hormone we mean a substance secreted into the blood stream which influences tissues and organs so as to differentiate and elaborate new cell types and new enzymes. While the retinoids of vision are secreted into the blood stream in support of the above roles, those destined for use in the visual process are transported in a more sophisticated manner that isolates them from the blood stream. 

James SY, Williams MA, Newland AC, and Colston KW (1999) Leukemia cell differentiation cellular and molecular interactions of retinoids and vitamin D. General Pharmacology 32, 143-54. 

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