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Because the receptor gene is expressed in several forms, it has many different (pleiotropic) effects in different parts of the body. When glucocorticoids bind to GR, its primary mechanism of action is the regulation of gene transcription. [5] [6] The unbound receptor resides in the cytosol of the cell. After the receptor is bound to ...
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone.When used as medication, it is known as hydrocortisone.. It is produced in many animals, mainly by the zona fasciculata of the adrenal cortex in an adrenal gland. [1]
RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST gene, and acts as a transcriptional repressor. [ 5 ] [ 6 ] [ 7 ] REST is expressly involved in the repression of neural genes in non-neuronal cells.
This allows for accessibility of the transcriptional machinery to specific gene regulatory regions, facilitating or inhibiting gene transcription. 4. Non-Genomic Signaling: In addition to classical genomic actions, steroid hormone receptors can initiate rapid, non-genomic signaling pathways in the cytoplasm or at the cell membrane.
The goal is to normalize the production of 21-hydroxylase, the enzyme encoded by CYP21A2. Providing a working copy of this gene may improve adrenal hormone synthesis and subsequently normalize cortisol and aldosterone production. [253] Currently, gene replacement therapy for CAH is still at an early stage of research and development.
There is ongoing research on how Genetic variants in the CYP21A2 gene may lead to pathogenic conditions. A variant of this gene has been reported to cause autosomal dominant posterior polar cataract, suggesting that steroid 21-hydroxylase may be involved in the extra-adrenal biosynthesis of aldosterone and cortisol in the lens of the eye. [72]
In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Two transcript variants encoding the same protein have been found for this gene.
Glucocorticoids may also inhibit the rates of POMC gene transcription and peptide synthesis. The latter is an example of a slow feedback loop, which works on the order of hours to days, whereas the former works on the order of minutes. The half-life of ACTH in human blood is reported to be between ten and 30 minutes. [6] [7] [8]