11-Beta hydroxysteroid dehydrogenaseHSDB2 expression is also found in the brainstem in a small, aldosterone-sensitive subset of neurons located in the nucleus of the solitary tract referred to as HSD2 neurons. In these tissues, HSD11B2 oxidizes the glucocorticoid cortisol 11b hydroxysteroid dehydrogenase type 2 the inactive metabolite cortisonethus preventing illicit activation of the mineralocorticoid receptor. This protective mechanism is necessary because cortisol circulates at fold higher concentrations than aldosterone, and binds with equal affinity to the mineralocorticoid receptor, thereby out-competing aldosterone in cells that do not produce HSD11B2. This glucocorticoid-inactivating enzyme is also expressed in tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, as well as parts of the developing brain, including the rhombencephalic progenitor steroid cycle planner excel that oxandrolon polska apteka into cerebellar granule cells. Inhibition of this enzyme, for example by a compound in liquorice, results 11b hydroxysteroid dehydrogenase type 2 a condition known as pseudohyperaldosteronism. A genetically inherited deficiency of HSD11B2 is the underlying cause of the syndrome of apparent mineralocorticoid excess.
WikiGenes - HSD11B2 - hydroxysteroid (beta) dehydrogenase 2
Providing cutting-edge scholarly communications to worldwide, enabling them to utilize available resources effectively. We aim to bring about a change in modern scholarly communications through the effective use of editorial and publishing polices. Cancer is the second most common cause of death in the world, and primary prevention remains the best approach to reducing overall morbidity and mortality. Glucocorticoids induce cancer cell apoptosis and are endogenous, potent COX-2 inhibitors.
Cancers are leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8. Primary prevention remains the best approach to reducing overall morbidity and mortality. COX-2 derived PGE2 has been reported to promote tumor growth through stimulation of cell proliferation, cell migration, cell invasion, angiogenesis and immunosuppression . COX-2 was initially described as an inflammatory-mediated cyclooxygenase. COX-2 plays an important role in tumor cell growth and in cancer metastasis .
COX-2 expression increases not only in the CRC and lung cancer, but to even higher levels in hepatic metastases . COX-2 expression is sensitive to glucocorticoid inhibition. Glucocorticoids GCs are the most potent, endogenous, specific COX-2 inhibitors, acting to suppress COX-2 expression through stimulating glucocorticoid receptors . Glucocorticoids are produced in the zona fasciculata middle cortical layer of the adrenal gland. Activation of glucocorticoid receptors inhibits COX-2 expression primarily through three mechanisms: GCs have been used to treat diseases caused by an overactive immune system, such as allergies, asthma, and autoimmune diseases as well as a broad spectrum of hematologic malignancies, including leukemia, lymphoma, and myeloma due to their ability to induce apoptosis .
Recent studies found the inhibitory effect of GCs to COX-2 could suppress solid tumor growth, regress tumor mass, and prevent metastasis by blocking angiogenesis [19,20]. However, the undesirable side effects of immunosuppression limit their application in cancer chemoprevention and chemotherapy.
Circulating glucocorticoid levels are regulated by the hypothalamo-pituitary-adrenal axis . Peptide corticotropin-releasing hormone CRH released from the hypothalamus following stressors stimulates the release of adrenocorticotropic hormone ACTH from the anterior pituitary, which in turn stimulates the adrenal gland to secrete glucocorticoids. When blood concentrations of glucocorticoids rise above a certain threshold, CRH secretion is inhibited from the hypothalamus, leading to turning off of ACTH secretion and subsequent turning off of glucocorticoid secretion from the adrenal gland.
Interestingly, the incidence of intestinal tumors is higher in the colon than in the small intestine. Mouse adenocarcinoma CT26 cells demonstrate significant tumorigenic activity and express high levels of COX-2, and both their proliferation in vitro and the size and number of CT26 tumors in vivo are sensitive to COX-2 inhibition . The retinoblastoma protein Rb , a tumor suppressor, inhibits cell proliferation through its interaction with the E2F family of transcription factors and the resultant regression of genes that are essential for DNA synthesis .
The inactivation of retinoblastoma protein is a prerequisite for cell proliferation. Inactivation of Rb is achieved through cyclin-dependent protein kinase-mediated phosphorylation during cell cycle progression. Glucocorticoids may also inhibit tumor growth through suppression of the mTOR signal pathway [49,50]. In adenomas from these mice, p53 and p21 levels increased, with concomitant decrease in phosphorylation of retinoblastoma protein.
The lipoxygenase LOX pathway is another important pathway for metabolism of arachidonic acid. Dexamethasone has been reported to inhibit 5-LOX expression and its metabolite production [61,62]. Increased tumor active glucocorticoids also inhibit tumor development and growth through induction of G1 cell cycle arrest and inhibition of the mTOR pathway; 5.
Tissue prostaglandin levels are determined by both biosynthesis and catabolism. Therefore, it is possible that increased intracellular active endogenous glucocorticoids may inhibit tumorigenesis not only by inhibiting prostaglandin synthesis, but also by enhancing prostaglandin degradation; and finally 6.
Glucocorticoid also inhibit the activity of cPLA2, preventing potential shunting of arachidonic acid metabolism to other procarcinogenic metabolizing pathway such as the 5-lipoxygenase lipoxygenase pathway [,65]. The subsequent inhibition of the COX-2 pathway and induction of G1 cell cycle arrest through activation of retinoblastoma protein Rb, a tumor suppressor and inhibition of the mTOR pathway lead to inhibition of colorectal tumorigenesis.
Long-term excessive ingestion of licorice has been reported to induce hypokalemia and elevation of blood pressure in a subset of people . Although these side effects were not seen in animal experiments, studies did observe that the concentrations of glycyrrhizic acid increased levels of active glucocorticoid levels in the kidney . April 02, Accepted: April 25, Published: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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References World Cancer Report Frankfurt O, Rosen ST Mechanisms of glucocorticoid-induced apoptosis in hematologic malignancies: Curr Opin Oncol Int J Cancer Clin Cancer Res Curr Opin Pharmacol 3: J Clin Invest J Biol Chem Arch Biochem Biophys Adv Cancer Res J Steroid Biochem Mol Biol Mol Cell Endocrinol Horm Metab Res J Clin Endocrinol Metab Nat Rev Cancer 3: J Surg Res Cancer Biol Ther 3: Differential Effects Depending on Stress History.
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