1852-53-5Relevant articles and documents
Regio- And Stereo-chemical Effects in the Hydroboration of Δ2-Steroidal Allylic and Homoallylic Alcohols
Hanson, James R.,Liman, Mansur D.,Nagaratnam, Sivajini
, p. 282 - 283 (1997)
A comparison between the hydroboration of δ2-steroidal 1x-allylic and 5x-homoallylic alcohols reveals that whereas both have a stereochemical directing effect, only the allylic alcohol modifies the regiospecificity of the reaction.
Comparative studies of androgen metabolism in theca and granulosa cells of human follicles in vitro
Moon,Duleba
, p. 419 - 430 (1982)
In eight separate experiments, theca and granulosa were isolated from human follicles (5-25 mm in diameter) , and their capacities to metabolize radiolabelled testosterone in 24 hour cultures were assessed. Theca metabolized testosterone primarily to androstenedione, however significant aromatization to estradiol-17β and to estrone was also observed. Granulosa metabolized testosterone primarily to estradiol-17β and estrone, while smaller quantities were converted to androstenedione. In seven of these experiments, the intermediate of aromatization, 19-hydroxytestosterone, was identified. In six of these experiments, theca, when compared to granulosa, produced more androstenedione but less estradiol-17β and estrone. 5α-Reduced androgens were non-detectable or produced in small quantities. In a single experiment, metabolism of androstenedione was compared to metabolism of testosterone by both theca and granulosa. Theca metabolized androstenedione to testosterone in smaller quantities than testosterone to androstenedione. Granulosa metabolized androstenedione to testosterone in higher quantities than testosterone to androstenedione. Both theca and granulosa aromatized androstenedione more readily than testosterone.
A molecularly imprinted receptor for separation of testosterone and epitestosterone, based on a steroidal cross-linker
Gavrilovi?, Ivana,Mitchell, Karen,Brailsford, Alan D.,Cowan, David A.,Kicman, Andrew T.,Ansell, Richard J.
, p. 478 - 483 (2011)
A series of molecularly imprinted polymers have been prepared and investigated as stationary phases in high performance liquid chromatography for the separation of testosterone and epitestosterone using non-polar mobile phases. The polymers were imprinted using 5α-dihydrotestosterone as template, and all retain testosterone more strongly than its 17α-OH epimer. The best polymer was prepared using trifluoromethylacrylic acid as functional monomer (interacting with the template via hydrogen bonds), divinylbenzene as 'inert' cross-linker, and chloroform as porogen. It also included a steroid-based cross-linker, which may interact with the template via van der Waals interactions to lend additional 'shape selectivity'. A 250 × 4.6 mm column packed with this polymer gave baseline resolution of testosterone and epitestosterone (15 μg each) in under 20 min. Preparation of the steroid based cross-linker included the selective reduction of 5α- dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) to the 3α,17β-diol using K-selectride.
Glucosiduronidation and esterification of androsterone by human breast tumors in vitro
Raju,Kadner,Levitz,Kaganowicz,Blaustein
, p. 399 - 407 (1981)
The metabolism of 3H-androsterone was studied in homogenates (fortified with uridine 5'-diphosphoglucuronic acid and andenosine 3'- phosphate 5'-phosphosulfate) of eighteen breast tumors, one muscle underlying the primary breast carcinoma and metastatic axillary lymph nodes from a patient with suspected primary breast cancer. The major metabolites identified were less polar than androsterone. On saponification these lipoidal derivatives afforded androsterone as the only product (3 to 48%). Unmetabolized androsterone and lesser quantities of epiandrosterone, 5α-andorstane-3α, 17β-diol and 5α-androstane-3,17-dione comprised the free steroid fraction. Androsterone glucosiduronate was isolated (0.17-4.1%) from eight breast tumor homogenates and fromthe node tissue incubation (17%). There was no apparent correlation between glucuronyltransferase activity and histolpathology or estrogen receptor content.
STUDIES ON THE KINETICS OF THE INTERACTION OF 7α-HYDROXYTESTOSTERONE WITH THE STEROID 5α-REDUCTASE
Mittler, James C.
, p. 135 - 142 (1985)
Microsomal preparations from adult male rat testicular interstitial cells were incubated with tritiated testosterone.Added 7α-hydroxytestosterone, (7α,17β-dihydroxy-4-androsten-3-one), at levels which appear to exist in the adult testis, inhibited production of labelled 5α-reduced steroids in a graded fashion.This interaction is not competitive and occurs only at high substrate levels, such as those found in steroid-producing organs.Relationships to pubertal changes in steroid metabolism are discussed.
Role of human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C3) in the extrahepatic metabolism of the steroidal aromatase inactivator Formestane
Wan, Runlan,Kong, Xi,Yang, Youzhe,Tao, Siwen,Chen, Youyou,Teichmann, Alexander Tobias,Wieland, Frank Heinrich
, (2019/12/23)
The clinical use of the steroidal aromatase inhibitor Formestane (4-hydroxandrostenedione, 4-OHA) in the treatment of advanced ER+ breast cancer has been discontinued, and therefore, interest in this remarkable drug has vanished. As a C-19 sterol, 4-OHA can undergo extensive intracellular metabolism depending on the expression of specific enzymes in the corresponding cells. We used the metabolites 4β-hydroxyandrosterone, 4β-hydroxyepiandrosterone and its 17β-reduced derivative as standards for the proof of catalytic activity present in the cell culture medium and expressed by the isolated enzymes. All of the aldo-keto reductases AKR1C1, AKR1C2, AKR1C3 and AKR1C4 catalysed the reduction of the 3-keto-group and the Δ4,5 double bond of 4-OHA at the same time. Molecular docking experiments using microscale thermophoresis and the examination of the kinetic behaviour of the isolated enzymes with the substrate 4-OHA proved that AKR1C3 had the highest affinity for the substrate, whereas AKR1C1 was the most efficient enzyme. Both enzymes (AKR1C1and AKR1C3) are highly expressed in adipose tissue and lungs, exhibiting 3β-HSD activity. The possibility that 4-OHA generates biologically active derivatives such as the androgen 4-hydroxytestosterone or some 17β-hydroxy derivatives of the 5α-reduced metabolites may reawaken interest in Formestane, provided that a suitable method of administration can be developed, avoiding oral or intramuscular depot-injection administration.
Rapid probing of the reactivity of P450 monooxygenases from the CYP116B subfamily using a substrate-based method
Li, Ren-Jie,Xu, Jian-He,Yin, Yue-Cai,Wirth, Nicolas,Ren, Jiang-Meng,Zeng, Bu-Bing,Yu, Hui-Lei
supporting information, p. 8928 - 8934 (2016/10/13)
Developing a detailed understanding of the reactivity of self-sufficient Type IV P450 monooxygenases, four types of O-methylated substrates were designed as probes, including monoterpenes, cycloalkanes, aromatic compounds and steroids, and the efficiency of their oxyfunction was determined using a colorimetric assay which was based on the reaction between the enzymatic demethylation product, formaldehyde, and Purpald dye. The activity-based fingerprints of new P450RpMO, P450ArMO and P450CtMO (CYP116B members) indicated that CYP116B P450s preferentially oxidize substrates with aromatic components. Moreover, the hydroxylated products were detected based on the preference results. This rapid and efficient strategy, when coupled with GCMS, enables the exploration of the reactivity of other CYP116B members.
