T1 - Human Steroid Biosynthesis
T1 - Steroid biosynthesis and renal excretion in human essential hypertension
Steroid biosynthesis - an overview | ScienceDirect Topics
Steroid biosynthesis is an metabolic pathway that producessteroids from simple precursors. This pathway is carried out indifferent ways in thanin many other ,making the pathway a common target for and other anti-infective . In addition, steroidmetabolism in is thetarget of -lowering drugs such as .
CYP11A1 is a mitochondrial enzyme that catalyzes theconversion of cholesterol to pregnenolone. This represents thefirst reaction in the process of steroidogenesis in all steroidhormone-producing mammalian tissues () (). Low expression ofCYP11A1 may cause steroid biosynthesis disorders ().
Steroid biosynthesis : Wikis (The Full Wiki)
Based on the preceding discussion, several strategies to block T and DHT synthesis and/or action can be envisioned, and most of these have already found application in clinical practice (). Surgical orchiectomy, DES, leuprolide acetate, and bicalutamide are all successful examples of different strategies to block testicular T production or action, and dutasteride inhibits conversion of T to DHT by 5α-reductase enzymes. The problem with AR antagonists is that most are partial agonists or incomplete antagonists, and up-regulation of LH and thus T might overcome the blockade, prompting the development of more potent compounds such as MDV3100 . Gonadal suppression strategies fail to address the abundant DHEAS and DHEA derived from human adrenal gland, which are only 3 or 2 steps upstream of T (), with redundant pathways mediating these transformations . Adrenal androgen elimination in CRPC probably explains the additional therapeutic benefit of ketoconazole , a CYP17A1 inhibitor, and dexamethasone or prednisone, which suppress ACTH and thus adrenal DHEA(S) production .
Based on the paradigms described, damage to the pituitary (tumor, trauma, radiation) will lower LH, FSH, and ACTH production and therefore reduce production of T, E2, cortisol, DHEAS, and all the precursor steroids and metabolites as well. Surgical removal of the adrenal glands raises ACTH, which can be lowered with exogenous cortisol replacement. Gonadectomy will cause LH and FSH to rise, and androgen or estrogen replacement lowers LH but not FSH, since inhibin B remains absent. Similarly, natural menopause occurs when all follicles and thus granulosa cells are depleted, and estradiol production falls while LH and more specifically FSH rise. Long-acting GnRH agonists act by desensitizing the pituitary gonadotropes and suppressing LH (and FSH) and therefore T and E2 synthesis. Supraphysiologic doses of exogenous androgens and estrogens or progestins also lower LH, T, and E2 production—but not FSH—but directly exert hormone actions on the body. For example, high-dose DES, a potent estrogen, is used to treat prostate cancer by increasing negative feedback on the gonadal axis, which suppresses LH and thus T production. The estrogenic action of DES, however, causes gynecomastia in a high proportion of patients and predisposes to thrombotic events, limiting its utility. Similarly, dexamethasone or prednisone suppress ACTH and thus both cortisol and DHEAS synthesis. Steroid receptor antagonists relieve the negative feedback of these hormones and cause a rise in the tropic hormones from the pituitary and subsequently the endogenous steroids themselves.
Steroid Biosynthesis (Homo sapiens) - WikiPathways
The conversion of cholesterol to pregnenolone is generally the slowest, most complex, and acutely regulated step in steroid production . The side chain cleavage enzyme (P450scc or CYP11A1) uniquely catalyzes this transformation, which really involves three chemical steps, at a maximum rate of roughly 7 turnovers per minute, pathetically slow for an enzyme. In addition, access of cholesterol to CYP11A1 is restricted topologically within the specialized mitochondria of steroidogenic cells. The mobile pool of cholesterol capable of entering steroid biosynthesis resides on the outer mitochondrial membrane, whereas CYP11A1 and its cofactor protein ferredoxin reductase (FdxR) are attached to the inner mitochondrial membrane (). In the mitochondrial matrix, electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) channel from FdxR to a soluble iron-sulfur protein ferredoxin (Fdx) and then to CYP11A1. This reaction uses two electrons and one molecule of oxygen in each of three cycles to cleave cholesterol to pregnenolone. Every pulse of luteinizing hormone (LH) yields a corresponding pulse of T via the induction of intracellular cyclic adenosine monophosphate (cAMP), which “opens the gate” for cholesterol entry to the steroidogenic pathway. The familiar cosyntropin stimulation test also elicits a sharp rise in cortisol in 30 min, due to cAMP elevation and cholesterol mobilization. How does this rapid mobilization of cholesterol occur?
An important concept in steroid biosynthesis is that most steps are irreversible and that classes of endogenous steroid hormones are defined both by their biologic activities and their chemical structures. These structures, in turn, are determined by the activities of those enzymes catalyzing their biosynthesis, and the nomenclature is mercifully helpful for the novice in most cases. Most of these enzymes are cytochromes P450, and their naming is thus CYP followed by number, letter, and number (CYP17A1, CYP3A4, etc) . In addition, the 5α-reductase reactions are irreversible ().
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Biosynthesis and metabolism of steroid hormones by …
Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas
KEGG PATHWAY: Steroid hormone biosynthesis - …
Steroid Biosynthesis Flashcards | Quizlet
Microaerobic steroid biosynthesis and the molecular …
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16/08/2011 · As steroid biosynthesis requires ..
(iii) Female hormones estrone and estradiol are formed from testosterone and 4-androstene-3,17-dione by oxidative removal of the C19 methyl group and subsequent aromatization of ring A [MD:].
potentially due to O 2 limitation of the rate of steroid biosynthesis
Hanukoglu I: Steroidogenic enzymes:Structure, function, and role in regulation of steroid hormonebiosynthesis. J Steroid Biochem Mol Biol. 43:779–804. 1992. : :
Steroid Hormones: Chemistry, Biosynthesis, and …
AIs and CYP17A1 inhibitors will be widely used by oncologists, yet fellowship programs provide little training in steroid biosynthesis, compared with training in the biology of standard chemotherapies. Consequently, these drugs might be used without an appreciation of their caveats and pitfalls. The purpose of this review is to acquaint practicing oncologists with the fundamental principles and pathways of steroid biosynthesis, to improve their understanding of how and why these drugs work, and to alert these physicians to potential problems related to the drugs’ mechanisms of action.
@Cucurbitadienol | Steroid | Biosynthesis
Decreased expression and mutations of the CYP11family may influence the biosynthesis of steroid hormones. Inrecent years, the majority of studies of steroid hormones have beenperformed in breast cancer patients (–).However, studies have investigated the role of steroid hormones inprostate (), lung (), endometrial (), colon () and liver cancer (). Steroid hormones have been demonstratedto activate focal adhesion kinase, which regulates early actinreorganization in colon cancer cells (). Steroid hormones were not previouslyconsidered to be involved with lung function (); however, numerous studies have reportedthat steroid hormones are important in normal lung development andfunction () and in thepathogenesis of pulmonary diseases, including lung cancer (–). Astudy of prostate cancer validated the hypothesis that thebiosynthesis of steroid hormones downstream of CYPs contributes tothe progression of castration-resistant prostate cancer (). Steroid hormones may also be utilizedfor the treatment of endometrial cancer. For example, progestintherapy has been demonstrated as a viable treatment option for type1 endometrial cancer (). Thesestudies support the results of the present study, which indicatedthat steroid hormones are extremely important in numerous cancertypes. In conclusion, the CYP11 family, which may affect steroidbiosynthesis, is commonly involved in various types of cancer. Thepresent study provides novel ideas that indicate that, with thedevelopment of technology, the CYP11 family could used as biomarkeror drug target in the future research of cancers. Additional dataand experiments will help to determine whether the genes of CYP11family may be used as biomarkers in the diagnosis of various typesof cancer. The method of computer-aided drug design may be used tosimulate the interaction between the CYP11 family and chemicalmolecules, which will verify whether the CYP11 family could becomedrug targets.
Steroid Biosynthesis (Mus musculus) - WikiPathways
Pregnenolone is a type of endogenous steroid, and isthe forerunner of several steroids, including glucocorticoids,mineralocorticoids, progestogens, estrogens and androgens (). Furthermore, pregnenolone is abiologically active neurosteroid (). Pregnenolone is synthesized fromcholesterol, a transversion that requires hydroxylation at the C20and C22 positions of the side-chain and is performed by the enzymeCYP11A1, which is located in the mitochondria and is controlled byanterior pituitary tropic hormones. Cortisol (a glucocorticoidsteroid hormone) is composed by the zona fasciculata of the adrenalcortex. During stress or hypoglycemia, cortisol will be released tosuppress the immune system, to increase blood glucose, to decreasebone formation and to support the metabolism of carbohydrates, fatand protein (,). Aldosterone (a mineralocorticoidsteroid hormone) is formed by the zona glomerulosa of the adrenalcortex, and is important for blood pressure regulation (). Blood pressure is managed by processesthat occur in the distal convoluted tubules and collecting ducts ofthe nephron, which encourage the reabsorption of ions and water,the secretion of potassium, the conservation of sodium, and theincrease in water retention, blood volume and blood pressure().
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