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Anesthesiology Apr 1990The neuromuscular blocking effects and pharmacokinetics of ORG 9426, 1.5 mg/kg and ORG 9616, 1.2 mg/kg iv, two new nondepolarizing neuromuscular blocking drugs, were...
The neuromuscular blocking effects and pharmacokinetics of ORG 9426, 1.5 mg/kg and ORG 9616, 1.2 mg/kg iv, two new nondepolarizing neuromuscular blocking drugs, were studied in 28 cats (i.e., 14 cats with each drug) with and without renal pedicle ligation. A gas chromatographic assay was used to determine the concentrations of ORG 9426 and ORG 9616 and its desacetyl metabolites in plasma, urine, bile, and liver. The duration of neuromuscular blockade of both drugs was not altered by ligation of renal pedicles. Plasma clearance of ORG 9426 was slower in cats with ligated renal pedicles (P less than 0.01). With ORG 9616, mean elimination half-life was slower and mean residence time longer in cats with renal pedicle ligation. Otherwise, there was no significant differences with any pharmacokinetic variables in cats with and without renal pedicle ligation. Only 8.7 +/- 5.7% (SD) and 6.0 +/- 2.8% of an injected dose of ORG 9426 and ORG 9616 was excreted into the urine, respectively. Conversely, 54.4 +/- 9.2% and 52.4 +/- 9.2% of an injected dose of ORG 9426 and 35.7 +/- 12.2% and 46.8 +/- 9.7% of ORG 9616 were excreted into the bile in cats without and with renal pedicle ligation, respectively. Finally, 21.3 +/- 6.5% and 33.5 +/- 15.6% of ORG 9426 and 14.0 +/- 3.2% and 18.1 +/- 5.6% of ORG 9616 were in the liver 6 h after injection in cats without and with renal pedicle ligation respectively. The authors were able to account for the biodisposition of 84.4% and 85.9% of an injected dose of ORG 9426 in cats without and with renal pedicle ligation respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Androstanols; Animals; Biotransformation; Cats; Kidney; Liver; Neuromuscular Blocking Agents; Osmolar Concentration; Rocuronium; Time Factors; Vecuronium Bromide
PubMed: 1969717
DOI: 10.1097/00000542-199004000-00016 -
Anesthesiology Nov 2017
Topics: Androstanols; Humans; Masks; Neuromuscular Nondepolarizing Agents; Respiration; Rocuronium
PubMed: 29040100
DOI: 10.1097/ALN.0000000000001827 -
European Journal of Biochemistry Mar 1999Although enzymatic processes involved in the formation of active steroids are well known, less information is available about the enzymes responsible for the metabolism...
Although enzymatic processes involved in the formation of active steroids are well known, less information is available about the enzymes responsible for the metabolism of these hormones. Moreover, the expression of these catabolic enzymes, which include UDP-glucuronosyltransferases, may play a role in the regulation of the level and action of steroid hormones in steroid target tissues. Previous studies have shown that the cynomolgus monkey contains high levels of circulating androgen glucuronides, indicating that it represents the best animal model to study the glucuronidation of steroids in extrahepatic tissues. Two cDNA libraries were constructed from monkey liver and prostate mRNA, and a novel UDP-glucuronosyltransferase UGT2B cDNA, UGT2B19, was isolated from both libraries. The UGT2B19 cDNA is 2108 bp in length and contains an open reading frame of 1584 bp encoding a protein of 528 residues. The UGT2B19 cDNA clone was transfected into HK293 cells and a stable cell line expressing UGT2B19 protein was established. The activity of UGT2B19 on 3alpha-hydroxy and 17beta-hydroxy positions of steroids was demonstrated. The enzyme also conjugates xenobiotics including eugenol, 1-naphthol and p-nitrophenol. Kinetic analysis revealed that UGT2B19 glucuronidates steroids with Km values of 1.6, 2.6 and 4.3 microm for testosterone, etiocholanolone and 5beta-androstane-3alpha,17beta-diol, respectively. UGT2B19 transcript was detected, by specific reverse transcriptase-PCR analysis in the liver, ovary, prostate, colon, spleen, kidney, pancreas, brain, cerebellum, mammary gland and epididymis. The molecular characterization of simian UGT2B19 demonstrates relevance of using monkey as an animal model to study and understand steroid glucuronidation in extrahepatic target tissue.
Topics: Amino Acid Sequence; Androstane-3,17-diol; Animals; Base Sequence; Cells, Cultured; Cloning, Molecular; Etiocholanolone; Glucuronosyltransferase; Humans; Macaca fascicularis; Molecular Sequence Data; Phylogeny; RNA, Messenger; Testosterone
PubMed: 10102998
DOI: 10.1046/j.1432-1327.1999.00197.x -
The Journal of Investigative Dermatology Dec 1978In basal cell epitheliomas the testosterone metabolism pattern differs from that of the normal surrounding skin. There is a significant reduction in 5 alpha-reductase... (Comparative Study)
Comparative Study
In basal cell epitheliomas the testosterone metabolism pattern differs from that of the normal surrounding skin. There is a significant reduction in 5 alpha-reductase activity with a consequent decrease in production of dihydrotestosterone and androstanediols. By contrast the 17 beta-hydroxysteroid dehydrogenase activity shows no consistent change.
Topics: Aged; Androstane-3,17-diol; Androstenediols; Carcinoma, Basal Cell; Female; Humans; Male; Middle Aged; Oxidoreductases; Skin; Skin Neoplasms; Testosterone
PubMed: 722111
DOI: 10.1111/1523-1747.ep12556155 -
Clinical and Experimental Allergy :... Jun 2022
Superior effect of MP-AzeFlu compared to monotherapy with fluticasone propionate or azelastine on GILZ, MKP-1 and TTP anti-inflammatory gene expression in healthy and inflamed upper airway mucosa.
Topics: Androstadienes; Anti-Inflammatory Agents; Drug Combinations; Fluticasone; Gene Expression; Humans; Mucous Membrane; Phthalazines
PubMed: 35066955
DOI: 10.1111/cea.14099 -
General and Comparative Endocrinology Jul 2023Polar bears (Ursus maritimus) in the wild are under threat due to climate change, primarily loss of sea ice, and experience poor reproductive success in zoos. The polar...
Polar bears (Ursus maritimus) in the wild are under threat due to climate change, primarily loss of sea ice, and experience poor reproductive success in zoos. The polar bear is a seasonally polyestrous species that exhibits embryonic diapause and pseudopregnancy, complicating characterization of reproductive function. Fecal excretion of testosterone and progesterone have been studied in polar bears, but accurately predicting reproductive success remains difficult. Dehydroepiandrosterone (DHEA) is a steroid hormone precursor correlated with reproductive success in other species, but has not been well studied in the polar bear. The purpose of the present study was to characterize the longitudinal excretion of DHEAS, the sulfated form of DHEA, from zoo-housed polar bears using a validated enzyme immunoassay. Lyophilized fecal samples from parturient females (n = 10), breeding non-parturient females (n = 11), a non-breeding adult female, a juvenile female, and a breeding adult male were investigated. Five of the breeding non-parturient females had been previously contracepted, while six were never contracepted. DHEAS concentrations were closely associated with testosterone concentrations (p < 0.05, rho > 0.57) for all reproductive statuses. Breeding females exhibited statistically significant (p < 0.05) increases in DHEAS concentration on or near breeding dates, which were not observed outside of the breeding season, or in the non-breeding or juvenile animals. Breeding non-parturient females exhibited higher median and baseline DHEAS concentrations than parturient females over the course of the breeding season. Previously contracepted (PC) breeding non-parturient females also exhibited higher season-long median and baseline DHEAS concentrations than non-previously (NPC) contracepted breeding non-parturient females. These findings suggest that DHEA is related to estrus or ovulation in the polar bear, that there is an optimal DHEA concentration window, and concentrations exceeding that threshold may be associated with reproductive dysfunction.
Topics: Animals; Female; Male; Ursidae; Dehydroepiandrosterone Sulfate; Reproduction; Testosterone; Estrus; Dehydroepiandrosterone
PubMed: 36940836
DOI: 10.1016/j.ygcen.2023.114276 -
European Journal of Biochemistry Aug 1980The present study applied the twin-ion technique of gas chromatography/mass spectrometry to establish 7 alpha-hydroxylation of 5 alpha-androstane-3 beta, 17 beta-diol by...
C19-Steroid metabolism by canine prostate, epididymis and perianal glands. Application of the twin-ion technique of gas chromatography/mass spectrometry to establish 7 alpha-hydroxylation.
The present study applied the twin-ion technique of gas chromatography/mass spectrometry to establish 7 alpha-hydroxylation of 5 alpha-androstane-3 beta, 17 beta-diol by canine prostate, epididymis and perianal glands. 5 alpha-[4-14C, 7 beta-2H0.52]Androstane-3 beta, 17 beta-diol (0.5 microM) was incubated for 60 min at 37 degrees C with minced canine prostate and epididymis in 50 ml 0.067 M phosphate buffer (pH 7.4) containing NADPH (0.2 mM). The principal radioactive metabolite fraction was isopolar in thin-layer chromatography with 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol and contained 24% (prostate incubation) and 23% (epididymis incubation) of the radioactivity added. Following gas chromatography of the trimethylsilyl ether derivative of these metabolites, the peak with the retention time of the derivative of 5 alpha-androstane-3 beta, 7 alpah, 17 beta-triol yielded a mass spectrum consistent with that of the authentic standard triol and gave the characteristic twin-ion, though with some loss of deuterium. Incubation of 5 alpha-[4-14C, 7 beta-2H0.46]dihydrotestosterone (7 microM) and minced canine perianal glands and NADPH (0.2 mM) gave in 5% yield a transformation product with an RF-value of 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol. One half of the chromatographic fraction was subjected to gas chromatography/mass spectrometry as the free steroid, the other as the CrO3-oxidation product. The site of hydroxylation was identified as 7 alpha from the gas chromatography retention time of the free 7 beta-deuterated (twin-ion) triol and mass-spectrometry loss of deuterium in the 3,7,17-trione produced by mild CrO3 oxidation. Results of a comparative study of the metabolism of [4-14C]testosterone and 5 alpha-dihydro[4-14C]-testosterone with minced canine perianal glands and shoulder skin showed that, whereas both tissues contain a high level of 3 beta-hydroxysteroid oxidoreductase, only the perianal glands were able to transform radioactive testosterone to the 5 alpha-reduced derivatives and thence to the 7 alpha-hydroxylated product.
Topics: Androgens; Androstane-3,17-diol; Animals; Carbon Radioisotopes; Deuterium; Dihydrotestosterone; Dogs; Epididymis; Gas Chromatography-Mass Spectrometry; Hydroxylation; Male; Organ Specificity; Perianal Glands; Prostate; Skin; Testosterone
PubMed: 7408872
DOI: 10.1111/j.1432-1033.1980.tb04776.x -
Chemical & Pharmaceutical Bulletin May 2002Two androstane alkaloids were isolated from the musk of Moschus moschiferus. The structures were elucidated to be 3alpha-ureido-androst-4-en-17-one (1) and...
Two androstane alkaloids were isolated from the musk of Moschus moschiferus. The structures were elucidated to be 3alpha-ureido-androst-4-en-17-one (1) and 3alpha-ureido-androst-4-en-17beta-ol (2) by two-dimensional NMR analysis (HMQC, 1H-1H COSY, HMBC, and NOESY).
Topics: Alkaloids; Androstanes; Animals; Deer; Exocrine Glands; Fatty Acids, Monounsaturated; Magnetic Resonance Spectroscopy; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Infrared
PubMed: 12036025
DOI: 10.1248/cpb.50.663 -
Endocrinology May 2012The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis...
The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression.
Topics: Androstane-3,17-diol; Animals; Cell Line; Cells, Cultured; Estradiol; Gene Expression; Hypothalamus; Mice; Neurons; Oxytocin; Promoter Regions, Genetic
PubMed: 22434086
DOI: 10.1210/en.2011-1002 -
BMC Public Health Feb 2008Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small.
BACKGROUND
Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small.
METHODS
In a nationally representative sample of 1,262 men participating in the morning examination session of phase I (1998-1991) of the third National Health and Nutrition Examination Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones were measured following a standardized protocol.
RESULTS
After adjustment for age and race-ethnicity, higher cadmium levels were associated with higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for smoking status and serum cotinine, none of the hormones maintained an association with urinary cadmium (each p-trend > 0.05).
CONCLUSION
Urinary cadmium levels were not associated with sex steroid hormone concentrations in a large nationally representative sample of US men.
Topics: Androstanes; Cadmium; Cross-Sectional Studies; Estradiol; Humans; Male; Middle Aged; Prostatism; Sex Hormone-Binding Globulin; Smoking; Testosterone
PubMed: 18294394
DOI: 10.1186/1471-2458-8-72