The metabolism of 17beta-estradiol-3-glucosiduronate and estrone-3-glucosiduronate in the rabbit.

[6, 7-3H]-17beta-Estradiol-3-glucosiduronate, [6, 7-3H]-estrone-3-glucosiduronate or [6, 7-3H]-estrone was administered intravenously into the rabbit, and analysis and identification of the urinary metabolites were carried out. In either case, the major urinary metabolite was found to be a diconjugate. The sequential enzymic hydrolysis indicated that this diconjugate was glucosiduronate-N-acetyglucosaminide of 17alpha-estradiol. From these results, the conversion of the estrogen glucosiduronate into a diconjugate was thought a rather universal phenomenon in the rabbit.     

Different role of endothelium/nitric oxide in 17beta-estradiol- and progesterone-induced relaxation in rat arteries

The present study was aimed to examine the different role of endothelium/nitric oxide in relaxation induced by two female sex hormones, 17beta-estradiol and progesterone in rat isolated aortas and mesenteric arteries. The isometric force of each ring was measured with Grass force-displacement transducers in the organ bathes. 17beta-Estradiol induced both endothelium-dependent and -independent relaxation in the rat aortas but only the endothelium-independent relaxation in the rat mesenteric arteries. In contrast. progesterone induced both endothelium-dependent and -independent relaxation in the rat mesenteric arteries but only endothelium-independent relaxation in rat aortas. N(G)-Nitro-L-arginine methyl ester and methylene blue attenuated the relaxant response to 17beta-estradiol in the aortic rings or to progesterone in the mesenteric arteries. Pretreatment with L-arginine antagonized the effect of N(G)-nitro-L-arginine methyl ester on sex hormone-induced relaxation. The endothelium contribution to relaxation seems to only relate to lower concentrations of 17beta-estradiol and progesterone. In summary, the present results clearly demonstrate a different role of the functional endothelium in the relaxant response to 17beta-estradiol or progesterone in the conduit vessel (aorta) and the resistance vessels (mesenteric artery). Nitric oxide contributes largely to the endothelium-dependent relaxation induced by 17beta-estradiol in the isolated aortas or by progesterone in the mesenteric arteries.     

Identification of radioactive 17beta-estradiol-17-beta-D-glucuronide and 17alpha-estradiol-17-beta-D-glucuronide in the urine of the domestic fowl after intramuscular injection of [4-14C]estrone.

Two previously uncharacterized radioactive estrogen conjugates, 17beta-estradiol-17-beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17beta-D-glucopyranosiduronate) and 17alpha-estradiol-17beta-D-glucuronide (3-hydroxyestra-1,3,5(10)-trien-17alpha-yl-beta-D-glucopyranosiduronate), have been identified in small but significant amounts in avian urine and in a ratio of approximately 2:1 after intramuscular injection of [4-14C]estrone.     

Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.

The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.     

Synthesis of 5 alpha-androstane-3 alpha,17 beta-diol 3- and 17-glucuronides

The glucuronidation of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) was carried out by three different methods: The Koenigs-Knorr reaction using methyl-2,3,4-tri-O-acetyl-1 alpha-bromo-1-deoxy-beta-D-glucuronate, by employing methyl-2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-alpha-D-gl ucopyranuronate (imidate procedure), and by the reaction of 2,3,4-tri-O-acetyl-alpha-D-glucopyranuronate catalyzed by trimethylsilyl trifluoromethanesulfonate (triflate method). The Koenigs-Knorr method gave the beta-anomers of both the 3- and 17-glucuronides. The imidate procedure also resulted in the beta-anomers of the 3- and 17-glucuronides, but in lower yield. The triflate method, however, yielded only the alpha-anomers of the 3- and 17-glucuronides. The structural assignments of these compounds were made from NMR spectral data obtained with a 500 mHz instrument.     

Methandienone-I. A convenient method for the separation of 17alpha-methyl-17beta-hydroxyandrosta-i,4-dien-3-one and 17alpha-methyl-17beta-hydroxyanorosta-1,4,6-trien-3-one

17 α -Methyl-17 β -hydroxyandrosta-1,4-dien-3-one and 17α-methyl-17β-hydroxyandrosta-1,4, 6-trienone are found in the mother liquor of the reaction leading to the formation of the former from 17 α -methyl-17β -hydroxyandrosta-4-ene-3-one (I). This mother liquor usually discarded as waste product in the industrial production of 17α -methyl-17β -hydroxyandrosta-1,4-dien-3-one, can now be used for obtaining the two compounds separately using sodium metabisulfite.     

Metabolism of 5 alpha-androstane-3 beta,17 beta-diol to 17 beta-hydroxy-5 alpha-androstan-3-one and 5 alpha-androstan-3 alpha,17 beta-diol in the rat.

Significant metabolism of 5 alpha-androstane-3 beta,17 beta-diol to 17 beta-hydroxy-5 alpha-androstan-3-one was recorded in several tissues and organs from rats and humans. This bioconversion was further investigated in rat testis homogenates. 5 alpha-Androstane-3 beta,17 beta-diol was readily metabolized to 17 beta-hydroxy-5 alpha-androstan-3-one with NAD and/or NADP added as cofactors. When a NADPH generating system was included in the incubation, 5 alpha-androstane-3 beta,17 beta-diol was metabolized to 5 alpha-androstan-3 alpha,17 beta-diol. Only small amounts of 17 beta-hydroxy-5 alpha-androstan-3-one accumulated under the latter condition.     

The identification of 17 -hydroxy-17-methyl-1,4-androstadien-3-one as a metabolite of the anabolic steroid drug 17 -hydroxy-17-methyl-1,4-androstadien-3-one in man

The more polar of the two major urinary metabolites of methandrostenolone, 17β-hydroxy-17-methyl-1,4-androstadien-3-one, in man has already been identified as 6β-hydroxymethandrostenolone, 6β, 17β-dihydroxy-17-methyl-1,4-androstadien-3-one. The other metabolite has now been identified as the 17-epimer of methandrostenolone, 17α-hydroxy-17-methyl-1,4-androstadien-3-one. The compound was isolated from the freely extractable neutral fraction of urine following the administration of 5 mg of the drug to normal men. The relevant chromatographic fractions from thin layer and gas liquid systems were identified by carbon skeleton chromatography. The 17-epimer has been synthesised, details of which are included, and the previously unidentified metabolite was found to be identical with the synthetic compound.