Disease relevance of C01523

• Moreover, hypoxia in vivo induced constitutive androstane receptor (CAR) as well as CAR binding to the CYP3A6 oligonucleotide probe, but not the pregnane X receptor [1].
• Periploca sepium Bge, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. Followed the bioactivity-guided isolation, the most potent immunosuppressive compound, periplocoside E (PSE), a pregnane glycoside, had been identified from P. sepium Bge [2].
• Novel oxidative cleavage of C17-C20 bond in pregnane by a Pseudomonas sp [3].
• Time course and inhibition of stavaroside K, veratramine and cevine-induced hemolysis by other pregnane glycosides and Veratrum alkaloids [4].

High impact information on C01523

• After lyophilization, the 12,000 x g pellet converted the sterol into C19 androgens and corticosteroids, in addition to C21O2 pregnane derivatives [5].
• Physiologically, peripherally synthesised pregnane steroids derived from endocrine glands such as the adrenals and ovaries function as hormones by crossing the blood brain barrier to influence neuronal signalling [6].
• To exert their effect the receptors bind to the same direct repeat site (DR4) within the phenobarbital response element of the CYP2B1 promoter and to the same DR3 site in the pregnane X response element of CYP3A1 [7].
• The pregnane steroids are synthesized in the periphery by endocrine glands such as the adrenals and the ovaries, but are also made by neurons and glial cells in the central nervous system itself [8].
• For a variety of androstane and pregnane derivatives, inducation by 5alphaH steroids was as great as or greater than that by 5betaH compounds, in contrast to previous findings in chick embryo liver [9].

Biological context of C01523

• In CV-1 cell transactivation assays, mammalian pregnane X receptors activate the chicken phenobarbital-inducible enhancer units to the same extent as does chicken xenobiotic receptor, each receptor maintaining its species-specific ligand spectrum [10].
• Because no canonical responsive element for the PXR-RXR alpha heterodimer was observed in the 5'-flanking region of the construct, deletion analysis was used to identify a pregnane responsive region between base pairs -700 and -683; this 20-bp region contains the antioxidant response element (ARE) [11].
• Apoptosis was increased in HBE cells to a similar range as with the pure pregnane progestin, Org2058 [12].
• Furthermore, the antistress actions are flumazenil-resistant, reaffirming that there may be an increase in the levels of pregnane neurosteroids in vivo, which may act on a specific allosteric site on GABA-A receptors distinct from BZD site [13].
• Compared with E2-induced growth at 10(-10) M, pregnane and 19-nortestosterone derived progestagens at 10(-6) M alone did enhance cell growth in T47D-A cells up to 25 and 100% respectively, whereas in T47D-S cells they did not influence growth [14].

Anatomical context of C01523

• Early postnatal stimulation alters pregnane neurosteroids in the hippocampus [15].
• 5beta-pregnane compounds are potent depressors of the central nervous system [16].
• The pregnane derivatives hardly stimulated cell growth at 10(-6) M in MCF-7 B and L cells except for Org 2058 in B cells, whereas in M cells a statistically significant growth induction was observed except for PROG [17].
• An in vitro test system was standardized to study potentiality of five hormonally inert pregnane derivatives on growing trophoblasts isolated from ectoplacental cone (EPC) of day 8 hamster embryo [18].
• The pharmacological activities of 12 pregnane derivatives (4-15) were determined on gonadectomized male hamster flank organs and seminal vesicles as antiandrogens and as 5alpha-reductase inhibitors [19].

Associations of C01523 with other chemical compounds

• Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the GABA type A-receptor [20].
• Inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17alpha-hydroxylase/17,20-lyase (hereafter referred to as CYP17 ) could prevent androgen biosynthesis from both sources [21].
• Bosentan, a dual endothelin receptor antagonist, activates the pregnane X nuclear receptor [22].
• Regulation of the CYP3A4 gene by hydrocortisone and xenobiotics: role of the glucocorticoid and pregnane X receptors [23].
• The data illustrate the ability of the ESI techniques in the identification of pregnane glycosides, including the nature of the pregnane core, the kind of ester substituents, the types of sugar residues (hexose, deoxyhexose, dideoxyhexose, O-methyldeoxyhexose and O-methyldideoxyhexose), and the primary structure of the saccharide chain [24].

Gene context of C01523

• In vivo activation of the human CYP3A4 promoter in mouse liver and regulation by pregnane X receptors [25].
• RESULTS: The mean +/- standard error hepatic CYP3A activity of the study group was 3156 +/- 2794 pmol x min(-1) x mg(-1) of protein, and it was not associated with age, gender, medicinal use, CYP3A5 or pregnane xenobiotic receptor mRNA expression, or CYP3A5 genotype [26].
• Conversely, pregnane 16alpha-carbonitrile is a more potent activator of the rat and mouse PXR than the human and rabbit receptor [27].
• Chicken xenobiotic receptor, pregnane X receptor, and constitutive androstane receptor all bound to the CYP2H1 phenobarbital-inducible enhancer units in gel-shift experiments [10].
• Phylogenetic comparisons with nuclear receptors from other vertebrates revealed that lampVDR is a basal member of the VDR grouping, also closely related to the pregnane X receptors and constitutive androstane receptors [28].

Analytical, diagnostic and therapeutic context of C01523

• Upon administration, certain pregnane steroids produce clear behavioural effects including, anxiolysis, sedation, analgesia, anaesthesia and are anti-convulsant [8].
• While the findings with ALLOP emphasize the therapeutic potential of neurosteroid treatment during EtOH withdrawal, the gene mapping studies suggest that pregnane neurosteroid biosynthesis may represent a target for therapeutic intervention in the treatment of alcohol dependence [29].
• Electrospray ionization mass spectrometry for identification and structural characterization of pregnane glycosides [24].
• Screening for pregnane glycosides with immunological activities from the stems of Stephanotis mucronata by high-performance liquid chromatography/tandem mass spectrometry [30].
• Improved separation of some isomers and epimers of the pregnane series by thin-layer chromatography with repeated development [31].

References