Hormones gene activation

In the 1980s, advances in biotechnology had a considerable impact on steroid research. During this period, the mechanism of steroid hormone-activated gene regulation became more clearly defined. These mechanistic studies stiH receive considerable attention in the primary Hterature. 

A sequence stretch 300 base pairs upstream of the transcriptional start site suffices for most of the transcriptional regulation of the IL-6 gene (Fig. 1). Within this sequence stretch several transcription factors find their specific recognition sites. In 5 to 3 direction, AP-1, CREB, C/EBP 3/NF-IL6, SP-1 and NF-kB can bind to the promoter followed by TATA and its TATA binding protein TBP. Most enhancer factors become active in response to one or several different stimuli and the active factors can trigger transcription individually or in concert. For example, AP-1 is active upon cellular stress, or upon stimuli that tell cells to proliferate CREB becomes also active if cells experience growth signals, but also upon elevation of intracellular levels of cyclic adenosine monophosphate (cAMP), which occurs upon stimulation if so called hormone-activated G protein-coupled receptors. 

For example, a single hormone-activated gene induces the formation of many mRNA molecules and each mRNA molecule may be used to synthesize many enzyme molecules. Furthermore, the effects of hormones using this mechanism are prolonged. As long as the newly synthesized enzyme is active, the effect of the initiating hormone persists. 

The normal form of interaction between receptor and DNA requires the hormone to have broken the native structure of the receptor and the dimer to have been formed. That is to say, the receptor-DNA interaction comes after the hormone-receptor interaction. Nevertheless, situations have been described in vitro in which the receptor is able to be previously associated to the HRE. This situation occurs in vivo for the thyroid hormone receptors, in which case it seems that the hormone-free dimer acts as an expression repressor of genes dependent on these hormones (Evans et al. 1988). The arrival of the hormone activates the dimer in situ and inverts its role as regulator. 

Hormones and vitamins also play a role in regulation of ASBT. Both glucocorticoid receptor ligands and co-expression of the glucocorticoid receptor gene increased activity of ASBT, while there is also evidence that dihydroxy vitamin D binds directly to the vitamin D response element and increases expression of ASBT, leading to increased transport of bile acids into the enterocyte. ... 

For a hormone to have a specific effect on gene activity, any increase in enzyme activity must result from de novo synthesis by newly formed mRNA. This increase in enzyme activity may or may not precede any general increase in metabolic activity. From the foregoing discussion on chromatin activity, it is clear that plant hormones largely either increase the activity of polymerase I or increase the synthesis of total RNA s. Claims that the hormones "activate" chromatin-bound polymerases and "modulate" the number of active sites on the chromatin (21) have not been substantiated. There are only two known examples of hormone-induced synthesis of specific mRNA s. The classic example is the barley aleurone cells, in which GA treatment induces de novo synthesis and release of K-amylase (58, 59, 60), protease (61), and possibly as many as ten proteins (62). 

Two other new nuclear receptors have been shown to increase epidermal differentiation the LXR and the FXR. Farnesol and juvenile hormone activate the FXR leading to improved epidermal differentiation. Two genes encode for the LXR proteins, LXR alpha and LXR beta, and both are activated by various oxysterols the most potent being 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, 24(S) 25-epoxycholesterol and 7-hydroxy cholesterol. Cholestenoic acid also acts on this receptor. In vitro these agents also increased epidermal filaggrin levels.129,130... 

Retinoid X receptor (RXR) and orphan receptors are not accompanied by chaperone proteins. In the absence of hormone, they bind to their specific DNA sequence, repressing the gene. Upon activation by the hormone, they activate the transcription of the gene that they were repressing. 

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