Research Articles (Biochemistry)

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Browsing Research Articles (Biochemistry) by Subject "Adrenocortical hormones"

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    Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells
    (MDPI, 2014-03) Schloms, Lindie; Swart, Amanda C.
    Major rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2) and cytochrome P450 (P450) enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11β-hydroxylase (CYP11B1). All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The ihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions—dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes.
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    Salsola tuberculatiformis botschantzev and an aziridine precursor analog mediate the in vivo increase in free corticosterone and decrease in corticosteroid-binding globulin in female wistar rats
    (The Endocrine Society, 1999-05) Louw, Ann; Swart, P.
    Salsola tuberculatiformis Botschantzev causes prolonged gestation in sheep and contraception in rats. An active fraction isolated from the shrub, containing a highly labile hydoxyphenyl aziridine or precursor, and a more stable analog, compound A, inhibits sheep adrenal cytochrome P450c11. In addition, compound A has been shown to bind to and be stabilized by corticosteroid-binding globulin (CBG). Binding may result in concomitant displacement of endogenous steroids, which could contribute to the biological effects of these compounds. The present study was undertaken to establish which mechanism would predominate in female rats. Compound A significantly (P,0.01) displaced glucocorticoids, but not progesterone, from corticosterone in both S. tuberculatiformis (P , 0.05)- and compound A (P , 0.01)-treated rats was also significantly higher due to displacement from CBG. In addition, both ACTH and CBG concentrations were significantly (P , 0.05) lower than control values. The levels of the gonadotropins were also reduced during treatment, but only LH values significantly (P , 0.05) so. These results suggest that binding of the test substances to CBG in female rat plasma and concomitant displacement of endogenous corticosterone could be part of the contraceptive mechanism of S. tuberculatiformis and the aziridine precursor, compound A.
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    Steroid metabolome analysis in disorders of adrenal steroid biosynthesis and metabolism
    (Endocrine Society, 2019-07-11) Storbeck, Karl-Heinz; Schiffer, Lina; Baranowski, Elizabeth Sarah; Chortis, Vasileios; Prete, Alessandro; Barnard, Lise; Gilligan, Lorna; Taylor, Angela, E.; Idkowiak, Jan; Arlt, Wiebke; Shackleton, Cedric H. L.
    Steroid biosynthesis and metabolism are reflected by the serum steroid metabolome and, in even more detail, by the 24-hour urine steroid metabolome, which can provide unique insights into alterations of steroid flow and output indicative of underlying conditions. Mass spectrometry–based steroid metabolome profiling has allowed for the identification of unique multisteroid signatures associated with disorders of steroid biosynthesis and metabolism that can be used for personalized approaches to diagnosis, differential diagnosis, and prognostic prediction. Additionally, steroid metabolome analysis has been used successfully as a discovery tool, for the identification of novel steroidogenic disorders and pathways as well as revealing insights into the pathophysiology of adrenal disease. Increased availability and technological advances in mass spectrometry–based methodologies have refocused attention on steroid metabolome profiling and facilitated the development of high-throughput steroid profiling methods soon to reach clinical practice. Furthermore, steroid metabolomics, the combination of mass spectrometry–based steroid analysis with machine learning–based approaches, has facilitated the development of powerful customized diagnostic approaches. In this review, we provide a comprehensive up-to-date overview of the utility of steroid metabolome analysis for the diagnosis and management of inborn disorders of steroidogenesis and autonomous adrenal steroid excess in the context of adrenal tumors.