Corticosteroid pathway

The presence or absence of the enzyme, CYP17, is a major determinant of the fate of pregnenolone (or progesterone). The presence of the enzyme allows access to either the cortisol or the androgenic (sex steroid) pathways but blocks off the aldosterone synthetic pathway. The absence of the enzyme allows for the formation of progesterone and aldosterone but precludes the formation of either cortisol or androgens. (See following subsections on corticosteroid pathway and sex steroid pathway.)... 

Tantisira K G, Small K M, Litonjua A A, et al. (2005). Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma interaction between beta-agonist and corticosteroid pathways. Hum. Mol. Genet. 14 1671-1677. 

There are few definitive data to substantiate the efficacy of LTRA therapy in refractory asthma, except for patients with aspirin-sensitive asthma. This is a fairly uncommon form of asthma that occurs generally in adults who often have no prior (i.e., childhood) history of asthma or atopy, may have nasal polyposis, and who often are dependent upon oral corticosteroids for control of their asthma. This syndrome is not specific to aspirin but is provoked by any inhibitors of the cycloxygenase-1 (COX-1) pathway. These patients have been shown to have a genetic defect that causes... 

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

Mycophenolate mofetil is used together with cyclosporine and corticosteroids for the prophylaxis of acute organ rejection in patients undergoing allogeneic renal, or hepatic transplants. Compared with azathioprine it is more lymphocyte-specific and is associated with less bone marrow suppression, fewer opportunistic infections and lower incidence of acute rejection. More recently, the salt mycophenolate sodium has also been introduced. Mycophenolate mofetil is rapidly hydrolyzed to mycopheno-lic acid, its active metabolite. Mycophenolic acid is a reversible noncompetitive inhibitor of inosine monophosphate dehydrogenase, an important enzyme for the de novo synthesis of purines. As lymphocytes have little or no salvage pathway for purine... 

Pregnenolone leaves the mitochondria to become the obligatory precursor of corticosteroids and adrenal androgens. The biosynthetic pathway next branches into two separate routes. One route passes through progesterone and corticosterone to aldosterone, and the other... 

The classical progestins as well as the corticosteroids arc based on a steroid nucleus that incorporates a two-carbon side chain at the 17 position that often includes a carbonyl group at position 21. The hypothetical parent hydrocarbon has been assigned the name pregnane for purposes of nomenclature. While two classes of compounds, progestins and corticoids, share common biosynthetic pathways, their biological activities differ markedly. 

Corticosteroids block all the known pathways of eicosanoid synthesis, perhaps in part by stimulating the synthesis of several inhibitory proteins collectively called annexins or lipocortins. They inhibit phospholipase A2 activity, probably by interfering with... 

It is particularly worthy of note that the routes to corticosteroids, progestogens, oestro-gens, and androgens involve common precursors or partial pathways. This means that these processes need to be under very tight control if... 

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