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The adrenal corticosteroids, the mineralocorticoid aldosterone and glucocoticoid cortisol play roles in growth, development and maintenance of homeostasis. Upon their interaction with receptor proteins, mineralocorticoid (MR) and glucocoticoid (GR) receptors; these steroids influence the expression of mineralocorticoid and glucocoticoid target genes. The facts that (1) plasma levels of glucocorticoids is 100-1000 fold higher than those of aldosterone and (2) MR is inherently nonselective as it binds to both hormones with equal affinity; make the accessibility of MR to aldodosterone impossible. However, aldosterone is known to regulate renal sodium reabsorption and potassium secretion which is promoted by 11-Beta-hydroxysteroid dehydrogenase (11b-HSD), the latter conferring an aldosterone selectivity for MR. 11b-HSD is a microsomal short chain dehydrogenase /reductase (SDR) which catalyzes the inter-conversion of biologically active glucocorticoid (cortisol in human and corticosterone in rats and mice) with its inactive 11-oxo derivatives (cortisone and 11-dehydrocorticosterone). Two genetically unique and tissue specific isoforms (11b-HSD1 and 11b-HSD2) of 11b-HSD, have been identified. The decreased 11-beta-hydroxy oxidation of cortisol results in apparent mineralocorticoid excess (AME) disorder, which is manifested by hypertension, hypokalemia, low plasma renin activity, and responsiveness to spironolactone. AME is principally a disorder of juveniles and children with this condition oxidize cortisol to cortisone poorly but carry out the reverse process unimpaired. AME arises from mutations in the 11-beta-HSD2 genes. The glucocorticoids can also be produced locally by 11b-HSD1 and increased visceral accumulation of glucocorticoids results in visceral obesity, insulin resistant diabetes, hyperlipidemia and hyperphagia.

11-beta-HSD-1 (variously termed as HSD11L) is a ~35 kDa glycosylated membrane-protein, oriented into the lumen of
endoplasmic reticulum. This isoform is the sole 11b-reductase in the body and exerts two separate enzymatic activities: 11b-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) in vitro; however, in vivo, it acts mainly as reductase producing active cortisol. The enzyme also plays an important role in xenobiotic carbonyl compound detoxification processes. 11b-HSD1 is expressed in a wide array of tissues, with highest level in Liver and adipose tissues. The increased adipocyte 11b-HSD1 is a common mechanism for visceral obesity and metabolic syndrome. Although the deficiency in 11b-HSD1 activities is not related to AME; it results in a syndrome characterized by an increased adrenocorticotropic hormone (ACTH)-driven androgen production. In mouse, the over-all aa seq of 11b-HSD1 is approximately 18% identical to that of 11b-HSD2.

11-beta-HSD-2 is a ~41 kDa glycosylated membrane-protein present in the endoplasmic reticulum (ER). The N-terminal and C-terminal (catalytic domain) of 11b-HSD2 are in the lumen and cytoplasm of ER, respectively. 11b-HSD2 irreversibly catalyzes the dehydrogenation of active 11-b-hydroxycorticoids before they occupy mineralocorticoid receptors (MR) and thus confers aldosterone selectivity for inherently nonselective MR. The enzyme is expressed in a wide array of tissues, with highest level in mineralocorticoid target cells such as the renal and outer medullary collecting ducts. In mouse, rat and Human, the over-all aa sequence of 11b-HSD2 is >80% identical. In mouse, the over-all aa sequence of 11b-HSD2 is >80% identical to that of 11bHSD2.

ADI has produced highly specific rabbit polyclonal antibodies to 11b-HSD1 and 11b-HSD2 using the protein-specific peptide sequences. These antibodies should aid the studies related to obesity, diabetes, and Apparent Mineralocorticoid Excess disorder.

 

M= Mouse; R=Rat; H=Human; Ha=Hamster; Rb=Rabbit; B=Bovine; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein. *

** Expected antibody crossreactivity information is mostly based upon high (>80%) sequence conservation of antigenic/control peptides in various species. When antibody crossreactivity has actually been experimentally confirmed in various species, it will be mentioned in the appropriate data sheets.

"Neat Antisera or antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" IgG may be more suitable for immunohistochemical (IHC) applications and to reduce background in most immunological applications including ELISA and Western.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody blocking studies to establish antibody specificity.
Western blot +ve protein controls, where available, are semi-pure, pure or recombinant proteins that are formulated in SDS-PAGE sample buffer. They are recommended to be used for Western (load 10 ul/lane) for visualization with antibodies.
 

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