Agonist inhibitors are fully recommended-glucocorticoid receptor

Glucocorticoid receptor (GR) is widely present in various tissues and cells of the body. Almost all cells are its target cells. The binding site of each cell is mostly between 5000 and 20000, and its expression varies depending on the tissue. Not the same.

Glucocorticoid is a steroid hormone with important physiological and pharmacological effects such as anti-inflammatory, anti-allergic, anti-shock, immunosuppressive, etc., and is clinically used to treat many diseases. As a fat-soluble phospholipid, glucocorticoid enters the cell through the cell membrane through passive diffusion, combines with GR to form a hormone receptor complex, then translocates into the nucleus, binds to specific DNA binding sites, and initiates gene transcription Synthesize various proteins.

Mechanism

In the absence of glucocorticoids, GRa exists in the cytoplasm in the form of a receptor complex, which includes receptor polypeptides, two heat shock proteins (HSP) 90, and other protein components. The protein component prevents the receptor polypeptide from interacting with the nucleus in a free state. When GR is combined with glucocorticoids, the conformation of HSP90 changes. The GRa glucocorticoid complex separates from HSP90 and other protein components and enters the nucleus, where it binds to the stress response element (GRES) in the hormone response gene promoter region, thereby The transcription activity of the corresponding gene is enhanced and the corresponding protein is synthesized, such as lipocortin-1, adhesion molecule, endonuclease, neuroendopeptidase, angiotensin converting enzyme, etc., resulting in physiological and pharmacological effects.

Anti-inflammatory and immunosuppressive effects

Prevent or inhibit cell-mediated immune responses, delay allergic reactions, reduce the number of T lymphocytes, monocytes, and eosinophils, reduce the ability of immunoglobulin to bind to cell surface receptors, and inhibit the synthesis and release of interleukins , Thereby reducing the transformation of T lymphocytes to lymphocytes and reducing the expansion of immune response. Glucocorticoids also reduce the passage of immune complexes through the basement membrane, and can reduce the concentration of complement components and immunoglobulins.

Anti-toxic and anti-shock effect

Expansion of the constricted blood vessels increases myocardial contractility and cardiac output. Inhibit the production of inflammatory factors, reduce the sensitivity of blood vessels to vasoconstrictors, and improve microcirculation. Stabilize the lysosomal membrane and reduce the formation of myocardial inhibitor MDF. Improve the body’s tolerance to bacterial endotoxins.