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Nora R. Ceballos - One of the best experts on this subject based on the ideXlab platform.
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Relationship between steroidogenesis and spermiation in Rana catesbeiana and Leptodactylus ocellatus.
Journal of Comparative Physiology B, 2006Co-Authors: Cinthia Rosemblit, Andrea G. Pozzi, Nora R. CeballosAbstract:The present study employs an in vitro system to analyse the role of steroid hormones in hCG-induced spermiation in two species of anuran amphibian: Rana catesbeiana and Leptodactylus ocellatus. In vitro spermiation was induced with 10 IU hCG and the effect of different steroid-biosynthesis inhibitors was analysed. Cyanoketone (10−5 M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of androgen was significantly reduced. These results clearly showed that, in both species, spermiation-inducing action of hCG does not depend on the biosynthesis of 3-oxo-4-ene steroids. Moreover, when combined inhibitors, aminoglutethimide (10−5 M) plus Cyanoketone (10−5 M), were employed, spermiation evoked by hCG was not modified while hCG-induced androgen secretion significantly decreased. Additionally, none of the steroids used, progesterone, 17, 20α-dihydroxy-4-pregnen-3-one, testosterone and 5α-dihydrotestosterone, were able to induce spermiation in the absence of hCG, confirming that steroids are not involved in that process. In conclusion, as previously described in Bufo arenarum, in L. ocellatus and R. catesbeiana hCG-induced spermiation does not depend on steroid biosynthesis.
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human chorionic gonadotropin induced spermiation in bufo arenarum is not mediated by steroid biosynthesis
General and Comparative Endocrinology, 2000Co-Authors: Andrea G. Pozzi, Nora R. CeballosAbstract:This study employed an in vitro system to identify potential steroidal mediators of spermiation in Bufo arenarum. Testicular fragments were incubated for 2 h at 28 degrees. Spermiation was induced by 10 IU human chorionic gonadotropin (hCG) and the effect of different inhibitors of steroid biosynthesis was analyzed. Cyanoketone (10(-5)-10(-6) M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of 3-oxo-4-ene steroids and its reduced metabolites was inhibited by 95%. Aminogluthetimide at a concentration that inhibited testosterone biosynthesis (10(-4) and 10(-5) M) did not alter hCG actions. Similar results were obtained with spironolactone, an inhibitor of 17alpha-hydroxylase/17-20 lyase activity. No spermiation-inducing activity was found with different steroids (progesterone, 17-hydroxypregnenolone, 17, 20alpha/beta-dihydroxy-4-pregnene-3-one, estradiol, testosterone, etc.). It is concluded that spermiation induced by hCG is not steroid mediated in B. arenarum.
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Human chorionic gonadotropin-induced spermiation in Bufo arenarum is not mediated by steroid biosynthesis.
General and Comparative Endocrinology, 2000Co-Authors: Andrea G. Pozzi, Nora R. CeballosAbstract:This study employed an in vitro system to identify potential steroidal mediators of spermiation in Bufo arenarum. Testicular fragments were incubated for 2 h at 28°. Spermiation was induced by 10 IU human chorionic gonadotropin (hCG) and the effect of different inhibitors of steroid biosynthesis was analyzed. Cyanoketone (10−5–10−6 M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of 3-oxo-4-ene steroids and its reduced metabolites was inhibited by 95%. Aminogluthetimide at a concentration that inhibited testosterone biosynthesis (10−4 and 10−5 M) did not alter hCG actions. Similar results were obtained with spironolactone, an inhibitor of 17α-hydroxylase/17-20 lyase activity. No spermiation-inducing activity was found with different steroids (progesterone, 17-hydroxypregnenolone, 17,20α/β-dihydroxy-4-pregnene-3-one, estradiol, testosterone, etc.). It is concluded that spermiation induced by hCG is not steroid mediated in B. arenarum.
Andrea G. Pozzi - One of the best experts on this subject based on the ideXlab platform.
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Relationship between steroidogenesis and spermiation in Rana catesbeiana and Leptodactylus ocellatus.
Journal of Comparative Physiology B, 2006Co-Authors: Cinthia Rosemblit, Andrea G. Pozzi, Nora R. CeballosAbstract:The present study employs an in vitro system to analyse the role of steroid hormones in hCG-induced spermiation in two species of anuran amphibian: Rana catesbeiana and Leptodactylus ocellatus. In vitro spermiation was induced with 10 IU hCG and the effect of different steroid-biosynthesis inhibitors was analysed. Cyanoketone (10−5 M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of androgen was significantly reduced. These results clearly showed that, in both species, spermiation-inducing action of hCG does not depend on the biosynthesis of 3-oxo-4-ene steroids. Moreover, when combined inhibitors, aminoglutethimide (10−5 M) plus Cyanoketone (10−5 M), were employed, spermiation evoked by hCG was not modified while hCG-induced androgen secretion significantly decreased. Additionally, none of the steroids used, progesterone, 17, 20α-dihydroxy-4-pregnen-3-one, testosterone and 5α-dihydrotestosterone, were able to induce spermiation in the absence of hCG, confirming that steroids are not involved in that process. In conclusion, as previously described in Bufo arenarum, in L. ocellatus and R. catesbeiana hCG-induced spermiation does not depend on steroid biosynthesis.
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human chorionic gonadotropin induced spermiation in bufo arenarum is not mediated by steroid biosynthesis
General and Comparative Endocrinology, 2000Co-Authors: Andrea G. Pozzi, Nora R. CeballosAbstract:This study employed an in vitro system to identify potential steroidal mediators of spermiation in Bufo arenarum. Testicular fragments were incubated for 2 h at 28 degrees. Spermiation was induced by 10 IU human chorionic gonadotropin (hCG) and the effect of different inhibitors of steroid biosynthesis was analyzed. Cyanoketone (10(-5)-10(-6) M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of 3-oxo-4-ene steroids and its reduced metabolites was inhibited by 95%. Aminogluthetimide at a concentration that inhibited testosterone biosynthesis (10(-4) and 10(-5) M) did not alter hCG actions. Similar results were obtained with spironolactone, an inhibitor of 17alpha-hydroxylase/17-20 lyase activity. No spermiation-inducing activity was found with different steroids (progesterone, 17-hydroxypregnenolone, 17, 20alpha/beta-dihydroxy-4-pregnene-3-one, estradiol, testosterone, etc.). It is concluded that spermiation induced by hCG is not steroid mediated in B. arenarum.
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Human chorionic gonadotropin-induced spermiation in Bufo arenarum is not mediated by steroid biosynthesis.
General and Comparative Endocrinology, 2000Co-Authors: Andrea G. Pozzi, Nora R. CeballosAbstract:This study employed an in vitro system to identify potential steroidal mediators of spermiation in Bufo arenarum. Testicular fragments were incubated for 2 h at 28°. Spermiation was induced by 10 IU human chorionic gonadotropin (hCG) and the effect of different inhibitors of steroid biosynthesis was analyzed. Cyanoketone (10−5–10−6 M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of 3-oxo-4-ene steroids and its reduced metabolites was inhibited by 95%. Aminogluthetimide at a concentration that inhibited testosterone biosynthesis (10−4 and 10−5 M) did not alter hCG actions. Similar results were obtained with spironolactone, an inhibitor of 17α-hydroxylase/17-20 lyase activity. No spermiation-inducing activity was found with different steroids (progesterone, 17-hydroxypregnenolone, 17,20α/β-dihydroxy-4-pregnene-3-one, estradiol, testosterone, etc.). It is concluded that spermiation induced by hCG is not steroid mediated in B. arenarum.
Samuel J Danishefsky - One of the best experts on this subject based on the ideXlab platform.
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further expansion of the trans diels alder paradigm reductive alkylation of α Cyanoketones
ChemInform, 2011Co-Authors: Feng Peng, Robin E Grote, Samuel J DanishefskyAbstract:The ability of cis-fused α-cyano ketone Diels—Alder adducts (I) to undergo reductive methylation is investigated and the trans isomers are formed preferentially.
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further expansion of the trans diels alder paradigm reductive alkylation of α Cyanoketones
Tetrahedron Letters, 2011Co-Authors: Feng Peng, Robin E Grote, Samuel J DanishefskyAbstract:In the context of our “pattern recognition” approach as an aid in retrosynthetic analysis, we seek to discern substructural units – or motifs – within the target structures that are accessible through reasonable chemistry.1 Translating a target synthesis problem to the identification of such an accessible pattern (or patterns) may well be non-obvious but may, in the end, provide a particularly clear path for progress. Obviously, the value of this type of thought process grows as the number of accessible patterns (“safe havens”) increases. For example, recognition of a cis–fused junction in a bicyclic motif where at least one of the rings is 6-membered, typically suggests a classical Diels-Alder (DA)–based strategy. In an effort to expand the menu of useful patterns available, we recently undertook to study a possible trans–DA paradigm,2 The logic involves equipping a cyclic dienophile with a temporary activating group which enhances proclivities for formation of the bicicyclic adduct. Subsequent cleavage of this angular functionality and introduction of a new function at the same site, with overall inversion of configuration provides entry into the trans-fused series (Figure 1a).2a In pursuit of such a “trans–DA” paradigm, we have developed the capacity to rapidly construct trans-fused decalinoid motifs bearing angular methyl groups (Figure 1b).2c Thus, following DA cycloaddition, cis-fused α-bromoketones (1) are obtained. Exposure to lithium naphthalide (LN), and alkylation of the resultant enolate 2 with iodomethyl phenyl sulfide provides the angularly functionalized trans-fused adduct with high trans stereoselectivity in the very important octalin series (3). Following Raney Ni-mediated desulfurization, the angularly methylated trans-octalone system is in hand. While direct methylation also provides preferential transfused stereoisomer in the octalin series, the two-step protocol described above affords significantly higher trans-selectivities. Figure 1 Based on precedent from our α-bromoketone-based studies we hypothesized that it should also be possible to functionalize an analogous system bearing an angular cyano moiety (Figure 1c). It seemed likely that an α-cyanocyclenone system (cf. 4) would be a more reactive dienophile than is its corresponding α-bromo counterpart. Indeed, Liu and co-workers had reported that angularly cyanylated systems of the type 4 could be prepared by DA cycloaddition. Interestingly, they had reported that methylation of these compounds gave cis-fused products. However, the systems employed in their studies incorporated structural features which would be expected to dispose them toward cis-alkylation.3,4 Thus, we sought to explore the feasibility of converting cis-fused α-Cyanoketones (4) to trans-fused angularly alkylated products through recourse to the conditions which were successful in the α-bromoketone alkylation (see Figure 1b). In this context, we could also explore a tangential, nonetheless interesting, question, i.e. whether the distereoselectivies of enolate alkylations would be essentially the same starting with a α-bromo or α-cyano precursors. We first examined the direct methylation of α-Cyanoketones. Thus, a variety of cis-fused cycloadducts (4a–4d) readily underwent angular alkylation with MeI as an electrophile (Method A). As anticipated, trans-fused adducts were predominantly formed, albeit with moderate levels of selectivity (Table 1). The isolated cis- and trans- isomers were rigorously characterized through spectral comparison with known standards prepared by alternative methods.2c Table 1 Angular alkylation of α-Cyanoketones.a Having established the propensity of the enolate derived from the α-Cyanoketone to undergo alkylation to provide trans-fused adducts, we next sought to improve the selectivity ratios of the products (Table 1). As precedented,2c when iodomethyl phenyl sulfide5 was used as the electrophile, the product stereoselectivities were markedly improved. The levels of alkylation selectivity achieved under these conditions were quite similar to those observed in our previous study using α-bromoketone substrates. However, we note that, in general, the analogous α-bromoketones appear to afford somewhat higher trans:cis ratios.5 Finally, we examined the reductive allylation of α-Cyanoketones 4b and 4c, with allylbromide as the electrophile. The reactions were conducted under conditions that were previously reported to provide exclusively cis-fused products.3 Interestingly, we also obtained predominantly cis-fused adducts, though in our hands, isomeric mixtures (2:1 and 3:1, respectively) were observed (Scheme 1). Scheme 1 Allylation of α-Cyanoketones 4a and 4b. In summary, we describe herein a useful extension of our trans-Diels-Alder paradigm, through the development of a trans-selective reductive alkylation of cis-fused α-Cyanoketone Diels-Alder adducts. We note that our stereochemical assignments are fully supported by comparisons with known standards in the readily accessible (via Diels-Alder reactions) cis series. Moreover, the selectivities reported herein are entirely consistent with those obtained in the context of our analogous α-bromoketone alkylation protocol. The method described here has the major advantage in that it exploits the cyano substituted dienophile which is much more reactive than is the previously used bromo version. Experiments building upon these findings are in progress.
S Haider - One of the best experts on this subject based on the ideXlab platform.
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effects of camp forskolin and Cyanoketone on invitro oocyte maturation in the catfish clarias batrachus
Journal of Biosciences, 1997Co-Authors: Shail K Chaube, S HaiderAbstract:This study investigated the interactive effects of Cyanoketone (CK), an inhibitor of 3β-hydroxysteroid dehydrogenase on the effects of cAMP and forskolin (FK) on oocyte maturation inClarias batrachus using an in vitro incubation technique. When the oocytes were incubated in the presence of 1 Μg/ml 17α, 20β-dihydroxy-4-pregnen-3-one[l7α, 20Β-DP, the maturation-inducing steroid (MIS) of this species] for 6h, they matured [85.3 + 1.36% germinal vesicle breakdown (GVBD)] normally after additional incubation for 20–30 h in plain medium. On the other hand, exposure to 1.0 and 8 0 mM of cAMP after MIS stimulation caused significant inhibition of GVBD but lower concentrations (0.1 and 0.5 mM) of cAMP were noninhibitory. However, when the oocytes were preincubated for 1 h with 1 μg/mI CK, a significant inhibition in the percentage of GVBD was recorded including the lower concentrations of cAMP. FK, an activator of adenylate cyclase, could significantly induce GVBD at all of its concentrations (0.1, 0.5, 1.0 and 10.0 μM) in a dose- and time-dependent manner. However, when the oocytes were exposed to 1 μg/ml CK for 1 h, prior to FK stimulation, a complete inhibition of GVBD occurred but when CK treatment was given after the FK stimulation, only a partial inhibition of maturation was observed. Taken together, these data indirectly suggest that FK induces catfish oocyte maturation probably by stimulating follicular production of Δ4 steroid ( 17α,20 β-DP)through an adenylate cyclase-c AMP-mediated pathway, a mechanism identical to the gonadotropin-induced oocyte maturation.
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the in vitro effects of forskolin ibmx and Cyanoketone on meiotic maturation in follicle enclosed catfish clarias batrachus oocytes
Comparative Biochemistry and Physiology Part C: Pharmacology Toxicology and Endocrinology, 1996Co-Authors: S Haider, Shail K ChaubeAbstract:The effects of an adenylate cyclase activator (forskolin, FK), phosphodiesterase inhibitor (3-isobutyl-l-methyl-xanthine, IBMX) and an inhibitor of steroidogenesis (Cyanoketone, CK) on germinal vesicle breakdown (GVBD) in the catfish (Clarias batrachus) were investigated in vitro. In most of the experiments GVBD was induced by using 1 microgram/ml 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-DP), which is the maturation-inducing steroid (MIS) for this species. Adenosine 3':5'-cyclic monophosphate (cAMP) levels were also measured in the control, MIS-induced and/or FK- and IBMX-treated follicle-enclosed oocytes. MIS-induced GVBD was inhibited by FK (> or = 0.5 microM) or IBMX (> or = 1.0 mM), but oocyte exposed to 0.1 microM FK or 0.5 mM IBMX, after MIS stimulation, underwent GVBD. However, an inhibition of GVBD was recorded when the MIS-induced folliculated oocytes were preincubated with CK (1 microgram/ml) and subsequently treated with 0.1 microM FK. In the time course study, when the oocytes were stimulated by MIS for various time intervals and then treated with 1.0 microM FK or 1.0 mM IBMX, both the substances blocked maturation if they were added up to 12 hr after MIS. The extent of inhibition was gradually decreased and was completely removed after 30 hr of post-MIS stimulation. The stimulatory dose of 17 alpha,20 beta-DP (1 microgram/ml) not only induced GVBD (83.2 +/- 1.50%) in vitro but also reduced oocyte cAMP level (65.3 +/- 2.85 pmol/100 micrograms protein) significantly after 6 hr of incubation. However, FK (10.0 microM) or IBMX (1.0 mM) countered these effects and promoted the accumulation of cAMP in the oocytes; FK being more potent. On the other hand, when unstimulated full-grown but immature oocytes were cultured in vitro in the presence of different concentrations of FK, an induction of oocyte maturation was recorded in dose- and time-dependent manner. These results strongly suggest the involvement of cAMP in the regulation of catfish oocyte maturation.
George S Boyd - One of the best experts on this subject based on the ideXlab platform.
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the effect of azastene Cyanoketone and trilostane upon respiration and cleavage of the cholesterol side chain in mitochondria from bovine adrenal cortex
FEBS Journal, 2005Co-Authors: Stephen B Shears, George S BoydAbstract:Mitochondria prepared from bovine adrenal cortex and incubated with ADP and phosphate respired at about 45% of the rat observed in the presence of an uncoupler of oxidative phosphorylation; there was, however, little inefficiency in the reactions involved in the phosphorylation of ADP. Three inhibitors of the 3 beta-hydroxysteroid dehydrogenase (azastene, Cyanoketone and trilostane) were employed with a view to preventing pregnenolone metabolism and thus aiding the assay of cholesterol side-chain cleavage. Freshly made solutions of these inhibitors did not modify mitochondrial respiratory rates, at concentrations of 10 microM. In contrast, solutions maintained at 0-4 degrees C for one week subsequently inhibited the respiratory rate of uncoupled mitochondria. When fresh solutions of the inhibitors were used in the assays of cholesterol side-chain cleavage, 10 microM azastene did not significantly inhibit pregnenolone metabolism. Cyanoketone and trilostane were both significant inhibitors of pregnenolone metabolism, but 10 microM Cyanoketone reduced the initial rate of cholesterol side-chain cleavage by 50% in the presence of 10 mM malate, although this inhibition did not occur in the presence of 10 mM DL-isocitrate. Thus trilostane may be the preferred inhibitor of the 3 beta-hydroxysteroid dehydrogenase during studies of cholesterol side-chain cleavage in vitro.
