521-18-6Relevant articles and documents
A kinetic analysis of the 5α-reductases from human prostate and liver
Houston,Chisholm,Habib
, p. 355 - 369 (1987)
A kinetic analysis of the 5α-reductases from human liver and prostate is presented. Human prostatic 5α-reductase follows an ordered sequential mechanism in which NADPh binds first followed by testosterone. The order of release of products is DHT followed by NADP+. The apparent K(m) of prostatic 5α-reductase for testosterone is 0.0339 ± 0.006μM, while the apparent K(m) for NADPh is 2.52 ± 0.65μM. Human liver 5α-reductase also follows a sequential mechanism. The apparent K(m) of the liver enzyme is 0.110 ± 0.08μM; the apparent K(m) for NADPH is 6.2 ± 0.6μM. The fact that both the liver and prostatic 5α-reductases have a sequential kinetic mechanism rules out the possibility that the reduction of testosterone to dihydrotestosterone involves an electron transport system as previously proposed.
Comparative study of human steroid 5α-reductase isoforms in prostate and female breast skin tissues: Sensitivity to inhibition by finasteride and epristeride
Ranjan, Mala,Diffley, Penny,Stephen, Gita,Price, David,Walton, Terence J.,Newton, Russell P.
, p. 115 - 126 (2002)
Steroid 5α-reductase (5-AR) catalyses the reduction of testosterone (T) to dihydrotestosterone (DHT). The 5α-reductase found in human benign prostatic hyperplasia (BPH) has been compared with that found in human breast skin tissue in respect of sensitivity to inhibition by Finasteride and Epristeride. Kinetic studies showed the presence of two isoforms of 5α-reductase in benign prostatic hyperplasia indicated by low and high Km isoforms for testosterone, while female breast skin tissue contained only one isoform. The isoforms differ in their affinity for the inhibitors Finasteride and Epristeride, both compounds being more effective for the low Km 5α-reductase isoform than the high Km 5α-reductase of prostatic tissue, with Finasteride displaying competitive inhibition and Epristeride uncompetitive. Finasteride and Epristeride are also inhibitors of skin 5α-reductase, which possesses a comparable Ki for Finasteride to that of the low Km prostatic enzyme, but Epristeride was a less potent inhibitor of the skin enzyme relative to the prostate isoform. These results suggest that the inhibitors have therapeutic potential, other than for treatment of benign prostatic hyperplasia, for treating skin disorders influenced by the action of dihydrotestosterone and warrant further investigation.
Stereochemistry of Reduction by the 5α-Reductase Enzyme of Penicillium decumbens and the 1H NMR Assignment of 5α-Dihydrotestosterone
Holland, Herbert L.,Xu, Weili,Hughes, Donald W.
, p. 1760 - 1761 (1989)
Reduction of the alkenic bond of testosterone and androst-4-ene-3,7-dione by the 5α-reductase enzyme of Penicillium decumbens with trans stereochemistry.
Significance of the delta 5 and delta 4 steroidogenic pathways in the hamster preovulatory follicle.
Makris,Olsen,Ryan
, p. 641 - 651 (1983)
Isolated hamster granulosa cells and theca from preovulatory follicles were incubated in vitro for 2 and 6 h in the absence/or presence of LH and steroid substrates. The purpose of the experiments was to determine, in theca, the relative activities of the delta 5 and delta 4 pathways under controlled conditions, and to compare the ability of granulosa cells and theca to form progesterone from exogenous pregnenolone. The results of the experiments show that the delta 5 pathway in theca predominates before and up to 2 h after LH stimulation. The delayed effect of LH after 2 h is a switch from delta 5 to delta 4 as the major metabolic pathway. Progesterone formation from exogenous pregnenolone is 7 to 10 times greater in unstimulated granulosa cells than in theca. Acute effects of LH lead to increased conversion of exogenous pregnenolone to progesterone in granulosa cells but not theca. LH does, however, acutely stimulate the thecal conversion of DHEA to androstenedione. The longer term effect of LH in both cell types is to increase pregnenolone conversion to progesterone.
Spatial Localization and Quantitation of Androgens in Mouse Testis by Mass Spectrometry Imaging
Cobice, Diego F.,Livingstone, Dawn E. W.,MacKay, C. Logan,Goodwin, Richard J. A.,Smith, Lee B.,Walker, Brian R.,Andrew, Ruth
, p. 10362 - 10367 (2016)
Androgens are essential for male development and reproductive function. They are transported to their site of action as blood-borne endocrine hormones but can also be produced within tissues to act in intracrine and paracrine fashions. Because of this, circulating concentrations may not accurately reflect the androgenic influence within specific tissue microenvironments. Mass spectrometry imaging permits regional analysis of small molecular species directly from tissue surfaces. However, due to poor ionization and localized ion suppression, steroid hormones are difficult to detect. Here, derivatization with Girard T reagent was used to charge-tag testosterone and 5α-dihydrotestosterone allowing direct detection of these steroids in mouse testes, in both basal and maximally stimulated states, and in rat prostate. Limits of detection were ～0.1 pg for testosterone. Exemplary detection of endogenous steroids was achieved by matrix-assisted laser desorption ionization and either Fourier transform ion cyclotron resonance detection (at 150 μm spatial resolution) or quadrupole-time-of-flight detection (at 50 μm spatial resolution). Structural confirmation was achieved by collision induced fragmentation following liquid extraction surface analysis and electrospray ionization. This application broadens the scope for derivatization strategies on tissue surfaces to elucidate local endocrine signaling in health and disease.
Synthetic method of androstenone
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Paragraph 0087-0089; 0097-0099; 0102-0104; 0107-0109, (2021/05/12)
The invention relates to the field of medicine preparation, in particular to a synthetic method of androstenone. The preparation method comprises the following steps: S100, catalyzing testosterone by a catalyst, and carrying out hydrogenation addition reaction to obtain a compound I; S200, converting a 17-site hydroxyl group of the compound I into a halogen group or a sulfonate group which is easy to leave, so as to obtain a compound II; and S300, subjecting the compound II and alkali to an elimination reaction under the heating condition, namely, a dehalogenation reaction or a desulphonate reaction, so as to obtain androstenone. The synthesis method of androsteneone has the following beneficial effects: the raw materials are cheap and easy to obtain; the process is simple, the route is short, and the requirement on equipment is low; dangerous reagents and operation are avoided, and large-scale industrial production is easy to realize; and isomer impurities are not generated in the synthesis process, and the yield of the target product androsteneone is high.
Formation of 5α-dihydrotestosterone from 5α-androstane-3α,17β-diol in prostate cancer LAPC-4 cells – Identifying inhibitors of non-classical pathways producing the most potent androgen
Boutin, Sophie,Roy, Jenny,Maltais, René,Poirier, Donald
supporting information, (2019/11/26)
5α-Dihydrotestosterone (5α-DHT) possesses a great affinity for the androgen receptor (AR), and its binding to AR promotes the proliferation of prostate cancer (PC) cells in androgen-dependent PC. Primarily synthesized from testosterone (T) in testis, 5α-DHT could also be produced from 5α-androstane-3α,17β-diol (3α-diol), an almost inactive androgen, following non-classical pathways. We reported the chemical synthesis of non-commercially available [4-14C]-3α-diol from [4-14C]-T, and the development of a biological assay to identify inhibitors of the 5α-DHT formation from radiolabeled 3α-diol in LAPC-4 cell PC model. We measured the inhibitory potency of 5α-androstane derivatives against the formation of 5α-DHT, and inhibition curves were obtained for the most potent compounds (IC50 = 1.2–14.1 μM). The most potent inhibitor 25 (IC50 = 1.2 μM) possesses a 4-(4-CF3-3-CH3O-benzyl)piperazinyl methyl side chain at C3β and 17β-OH/17α-C[tbnd]CH functionalities at C17 of a 5α-androstane core.
The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1
Barnard, Lise,Nikolaou, Nikolaos,Louw, Carla,Schiffer, Lina,Gibson, Hylton,Gilligan, Lorna C.,Gangitano, Elena,Snoep, Jacky,Arlt, Wiebke,Tomlinson, Jeremy W.,Storbeck, Karl-Heinz
, (2020/07/21)
Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11β-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5β-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5β-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production.
Mild Deprotection of Dithioacetals by TMSCl/NaI Association in CH3CN
Yao, Yunxin,Zhao, Guangkuan,Hamze, Abdallah,Alami, Mouad,Provot, Olivier
, p. 5775 - 5779 (2020/08/17)
A mild process using a combination of TMSCl and NaI in acetonitrile is used to regenerate carbonyl compounds from a variety of dithiane and dithiolane derivatives. This easy to handle and inexpensive protocol is also efficient to deprotect oxygenated and mixed acetals as 1,3-dioxanes, 1,3-dioxolanes and 1,3-oxathianes quantitatively. As a possible extension of this method, it was also shown that nitrogenated substrates such as hydrazones, N-tosylhydrazones, and ketimines reacted well under these conditions to give the expected ketones in high yields. The methodology proposed herein is a good alternative to the existing methods since it does not use metals, oxidants, reducing agents, acidic or basic media, and keto-products were obtained in high to excellent yields.
Purified mCPBA, a Useful Reagent for the Oxidation of Aldehydes
Horn, Alexander,Kazmaier, Uli
, p. 2531 - 2536 (2018/03/21)
Purified mCPBA is a useful reagent for the oxidation of several classes of aldehyde. Although linear unbranched aliphatic aldehydes are oxidized to the corresponding carboxylic acids, α-branched ones undergo Baeyer–Villiger oxidation to formates. α-Branched α,β-unsaturated aldehydes provide enolformates and/or epoxides, which can be saponified to α-hydroxy ketones with shortening of the carbon chain by 1 carbon. Unbranched α,β-unsaturated aldehydes undergo an interesting Baeyer–Villiger oxidation/epoxidation/formate migration/BV oxidation cascade, which results in formyl-protected hydrates with an overall loss of two carbon atoms.
