Hormone gene activation effects

Steroid hormones and thyroid hormone carry out their effects by way of gene activation. In contrast to the protein/peptide hormones, which alter existing enzyme activity, these hormones induce the synthesis of new enzymes that then influence cellular metabolism. 

As with signal transduction and second messenger systems, the mechanism of gene activation allows for amplification of the hormone s effect. 

All of these hormones produce their effects after a characteristic lag period of 30 minutes to several hours—the time required for the synthesis of new proteins. This means that the gene-active hormones cannot be expected to alter a... 

The effects of these agents can persist for hours or days after the agonist concentration has been reduced to zero. The persistence of effect is primarily due to the relatively slow turnover of most enzymes and proteins, which can remain active in cells for hours or days after they have been synthesized. Consequently, it means that the beneficial (or toxic) effects of a gene-active hormone usually decrease slowly when administration of the hormone is stopped. 

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). 

A large number of studies (33) support the thesis (59) that the function of GA may be that of a derepressor of gene activity. Giberellic acid has significant effect on the synthesis of all species of RNA s (63, 64), but the formation of < —amylase does not depend on new synthesis of ribosomal and transfer RNA s. Unequivocal proof for GA-induced formation of transcripts was provided by the in vitro synthesis of peptides that are immuno-logically similar to -amylase on poly A+RNA templates that were. isolated from hormone-treated aleurone cells (65, 66, 67). Of particular significance is the finding that detectable levels of -amylase mRNA s were formed within 2 hr of treatment with GA. 

A second type of mechanism is illustrated by the malic enzyme and fatty synthetase systems. In such systems the effect of T3 on the accumulation of the specific mRNAs does not seem to depend only on direct gene activation by the T3-nuclear receptor. An amplification post-transcriptional mechanism seems to contribute to the accumulation of the specific mRNAs. Stabilization of the mRNA level is also differently modulated by other hormones and by the diet. 

As noted earlier, the velocity of any enzyme-catalyzed reaction is dependent upon the amount of effective enzyme present. Enzyme biosynthesis, like that of all proteins, is under genetic control, a long-term process. Biosynthesis of enzymes may be increased or decreased at the genome level. Various hormones can activate or repress the mechanisms controlling gene expression. Enzyme levels are the result of the balance between synthesis and degradation. This enzyme turnover may be altered by diverse physiological conditions, by hormone effects, and by the level of metabolites. 

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. However we also know of rare examples where binding of the ligand has an inhibitory effect on gene activation. 

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