Steroid Δ4-Reductases: their Physiological Role and Significance
Ronald Hobkirk in Steroid Biochemistry, 1979
As will be detailed, many androgen target tissues have the capacity to convert testosterone to 5α-dihydrotestosterone. This metabolite, which in some bioassays is more potent than testosterone itself, is probably the important intracellular andogen in these target tissues. The presence of the target tissue Δ4-5α-reductases accounts for a higher urine androsterone/etiocholanolone ratio (for the 14C metabolites of 14C-testosterone or for endogenous precursors) for men than for women.95 Approximately 40% of a dose of intravenously administered 14C-testosterone is converted to urine androsterone and etiocholanolone.95 The mean 14C-androsterone/14C-etiocholanolone ratios were 1.5 and 0.9 for young men and women, respectively, and 1.0 and 0.4 for old men and women respectively. The ratios were significantly different for both age groups. In support of the male androgen target tissues playing a significant role in the production of the 5α-metabolite androsterone was the finding that the ratios were not significantly different for boys and girls (1.7 and 1.9, respectively). There was no sex difference for the 5α/5β androstanediols for any of the age groups. That the sex hormone binding globulin influences the entry of testosterone into target tissues where Δ4-5α-reduction occurs is supported by the finding of less 5α-metabolites in situations where the level of the binding protein has been increased by estrogen administration.96
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Sheryl S. Smith in Neurosteroid Effects in the Central Nervous System, 2003
Evidence that acute exposure to AASs may have anxiolytic effects is provided by the study of Bing et al.81 in which male rats that received a single injection of testosterone before testing on Vogel’s conflict test accepted significantly more shocks than controls, consistent with an antianxiety action of testosterone. It is noteworthy that Bing et al.81 observe AAS-induced changes in anxiety within 24 h of a single injection of testosterone. First, it is unlikely that anything beyond physiological levels of testosterone would be present at 24 h after a single injection, given the rapid clearance of unesterified testosterone.4 However, if the anxiolytic effects were due to this testosterone treatment, then the narrow time frame, although not categorically excluding androgen receptor-dependent changes in gene expression, would be more consistent with a nongenomic mechanism of AAS action. Further evidence that androgens do indeed elicit rapid anxiolytic effects has been provided by a recent study that found that a single exposure to 500 yg of either testosterone, androsterone, or 3a-androstanediol reduced anxiety within 30 min.82 The anxiolytic effects of testosterone were blocked by co-injection of the GABAA receptor antagonists, bicuculline or picrotoxin, suggesting that the
Synthesis and Secretion of Plasminogen Activators and plasminogen Activator Inhibitor by Endothelial Cells
Cornelis Kluft in Tissue-Type Plasminogen Activator (t-PA): Physiological and Clinical Aspects, 1988
Various other agents have been reported to increase the production of plasminogen activator activity by bovine endothelial cells. When these cells are cultured in the presence of sitosterol110 or fucosterol,78 a 3- to 7-fold increase in intracellular and secreted PA activity was observed. This increase was shown by a nephelometric assay of the turbidity of a fibrin suspension. Fibrin autography after SDS polyacrylamide gel electrophoresis of endothelial cell conditioned medium confirmed the increase in plasminogen activator activity, and showed that the production of both t-PA and u-PA was increased. No effect was observed with several other steroids (including cholesterol110) and sex hormones (e.g., androsterone, testosterone, estrone, and estradiol78). The same authors111 reported that retinol increased the production of intra and extracellular PA activity 4- and 8-fold. When retinol was added together with L-ascorbic acid, the secretion of PA activity raised 20- to 50-fold; L-ascorbic acid alone increased the PA activity only 1.5-fold. This marked increased in PA activity was mainly due to 56 kDalton PA activity (u-PA, according to Shimonaka et al.78), but PA activity with a higher molecular weight (t-PA) was also increased.”111
Effects of night shift on the cognitive load of physicians and urinary steroid hormone profiles – a randomized crossover trial
Published in Chronobiology International, 2018
Wolf Osterode, Sandra Schranz, Galateja Jordakieva
Concerning our second aim of the study namely to investigate changes of steroid hormones after 24 h on duty (Table 3), mostly no significant dynamics were found. Only pregnanetriol and the ratio of androsterone/etiochoanolone were found to be reduced after 24 h on duty. Pregnanetriol is a urinary metabolite of 17-alpha-hydroxyprogesterone and a precursor in the biosynthesis of cortisol. While Vierhapper and Nowotny found an enormous enhanced excretion of glucocorticoids and main androgen metabolites after a night shift by male residents, Singer and Zumoff reported a suppression of these steroids, which would support the fact that stress and sleep deprivation suppress gonadal steroids. We may assume that stress and sleep deprivation were not extensive enough in our collective to exhibit clear steroid dynamics, which on the other hand justifies the reduction of longer time on duty and reduced responsibility for more medical departments in former times. The excretion ratio of androsterone/etiocholanolone indeed showed significant alterations implicating disturbances of an androgen metabolism. The change in the ratio of androsterone to etiocholanolone in favor of the latter implies hypothalamus involvement in androgen metabolism dynamics (Johnsen 1968).
Relative safety and quality of various dietary supplement products U.S. Service Members ask about
Published in Clinical Toxicology, 2022
Cindy Crawford, Abraham R. Walter, Bharathi Avula, Andrea T. Lindsey, Aimee M. Hunter, A. Khan Ikhlas, Patricia A. Deuster
Thirteen percent of the risky ingredients were on DEA’s Controlled Substances List as Schedule III drugs (including 19-Nor-5-androstenedione, 19-norandrosta-4,9-diene-3,17 Dione [35], androstenedione type of compounds [36], and androstadienedione (Boldione)); 33% were on the WADA list (DHEA (dehydroepiandrosterone), 1-androsterone, epiandrosterone, phenethylamine and its derivatives, including ingredients such as demelverine, and β-phenylethylamine), octodrine [37], and synephrine, which is currently on the WADA monitoring program [38]. Forty percent were either listed on the FDA Dietary Supplement Ingredient Advisory list [33] (5-alpha-hydroxy laxogenin, hordenine, an N Methyl Tyramine) or had FDA notices or warnings on record in regards to the ingredient (3,5-diiodo-l-thyronine [39], pregnenolone [40], theophylline [41,42], vinpocetine [43], yohimbine [44–50], and isopropylnorsynephrine [51]). Twenty-seven percent of these ingredients are currently prohibited by the DoD as of 2021. (Table 1; Supplemental File B) Some ingredients were included on multiple lists and some products listed multiple risky ingredients as shown in Table 1 and Supplemental File B.
Disruptions in the reproductive system of female rats after prenatal lipopolysaccharide-induced immunological stress: role of sex steroids
Published in Stress, 2019
V. M. Ignatiuk, M. S. Izvolskaya, V. S. Sharova, S. N. Voronova, L. A. Zakharova
The rats were killed at PND80 by conscious decapitation. Trunk blood samples were obtained and serum separated to detect testosterone and estradiol concentrations using a direct ELISA kit (Diagnostics Biochem Canada Inc., Canada), according to the manufacturer’s instructions (Check, Ubelacker, & Lauer, 1995). Intra- and inter-assay coefficients of variations were <17% for testosterone and 10% for estradiol; the minimum detectable concentrations were 0.17 and 10 pg/ml, respectively. The following compounds were tested for cross-reactivity with the estradiol ELISA kit, where estradiol cross-reacted at 100%, estriol—1.6%, estrone—1.3%, progesterone—0.1%, cortisol—0.1%. For the ELISA kit the cross–reactivity for testosterone was 100%, 5α-DHT—5.2%, androstenedione—1.4%, androstanediol—0.8%, progesterone—0.5%, androsterone—0.1%.
Related Knowledge Centers
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- 17Β-Hydroxysteroid Dehydrogenase