Hormones retinoic acid

The signal crosses the membrane and activates gene transcription. Signals for soluble receptors include steroid hormones, retinoic acid, thyroid hormone, and vitamin D. 

Retinoid Hormones Retinoids are potent hormones that regulate the growth, survival, and differentiation of cells via nuclear retinoid receptors. The prohormone retinol is synthesized from vitamin A, primarily in liver (see Fig. 10-21), and many tissues convert retinol to the hormone retinoic acid (RA). 

Glucuronidation is an important step in the elimination of many important endogenous substances from the body, including bilirubin, bile acids, steroid hormones, thyroid hormones, retinoic acids, and biogenic amines such as serotonin. Many of these compounds are also substrates for sulfonyltransferases (SULTs) (2). 

Lipophilic hormones that use intracellular gene-specific transcription factors include the steroid hormones, thyroid hormone, retinoic acid (active form of vitamin A), and vitamin D (Fig. 11.8). Because these compounds are water-insoluble, they are transported in the blood bound to serum albumin, which has a hydrophobic binding pocket, or to a more specific transport protein, such as steroid hormonebinding globulin (SHBG) and thyroid hormone-binding globulin (TBG). The intracellular receptors for these hormones are structurally similar and are referred to as the steroid hormone/thyroid hormone superfamily of receptors. 

Finally, steroid hormones, retinoic acid, eicosanoids, some NEFA, etc., can bind to nuclear receptors to activate transcription factors. For instance, retinoic acid can activate retinoic acid receptor to control differentiation and proliferation of many types of cells during development [53]. 

Umesono K, Murakami KK, Thompson CC, Evans RM (1991) Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65 1255-1266 Carlberg C (1995) Mechanisms of nuclear signalling by vitamin D3 interplay with retinoid and thyroid hormone signalling. EurJ Biochem 231 517-527... 

Brent et al., 1989] Brent, G. A., Dunn, M. K., Harney, J. W., Gulick, T., and Larsen, P. R. Thyroid hormone aporeceptor represses Ta inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1 (1989) 329-336 [Cevc and Marsh, 1987] Cevc, G., and Marsh, D. Phospholipid Bilayers Physical Principles and Models. John Wiley Sons, New York, 1987. 

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

Beside coactivators so-called corepressors exist that are bound to transcription factors such as nuclear receptors and inhibit the initiation of transcription. These factors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), which interact with nuclear receptors and serve as platforms for complexes containing histone deacetylases (HDACs). These enzymes cause the reversal of histone acetylation of histones leading to a tightening of chromatin and enhancing its inaccessibility for RNA polymerase containing complexes. 

Kang et al. [23] compared the clinical, histologic, and molecular responses of normal human skin to topical retinol with that of retinoic acid. Application of retinol and retinoic acid produced epidermal thickening. However, retinol produced less erythema compared with retinoic acid. The authors suggest that these data are compatible with the idea that retinol may he a pro-hormone of retinoic acid. 

Since the theory and medical applications of collagen sponge were described by Chvapil et al. (52-54), they have been used to deliver steroid hormones (55), the anticancer drugs trans-retinoic acid (TRA) (56,57), and 5-fluorouracil (5-FU) (58), and antibiotics (59). 

Nuclear Receptors Retinoic Acid Receptor Thyroid Hormone Receptor... 

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

Barres BA, Lazar MA, Raff MC 1994 A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120 1097-1108 deNooij JC, Letendre MA, Hariharan IK 1996 A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell 87 ... 

The genes that respond to a specific hormone contain identical HRE (Fig. 1.6). Normally, it is a matter of short nucleotide sequences pentamers or hexamers. In the case of the ER, the sequences are found repeated in inverse order in the same strand of DNA (palindromic, or symmetrically legible sequences 5 GGACA-nnn-ACAGG 3 n is any nucleotide). In the case of the thyroid hormones and retinoic acid, the HRE at times are presented like two repeated sequences in the same order (direct repetition GGACA-GGACA). 

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