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D C Collins

Publications and source records attributed to D C Collins.

At least 127 records · Page 7Linked to original sources

Evidence for the simultaneous uptake and release of certain estrogens by the splanchnic area in the dog.

Splanchnic extractions of total radioactivity, unconjugated radioactive estrogens, radioactive estrone glucosiduronate, and radioactive estradiol-17beta glucosiduronate(s) were determined in dogs following the infusion of (3H)estrone glucosiduronate and of (3H)estrone. Splanchnic extractions of radioactive estradiol-17alpha-3-glucosiduronate were determined after (3H)estrone glucosiduronate infusion. The mean splanchnic extractions of total radioactivity after (3H)estrone glucosiduronate and (3H)estrone infusions were positive and similar (42.2 +/- 2.4% (SE) and 34.9 +/- 2.4% (SE), respectively). The mean splanchnic extraction of unconjugated radioactive estrogens after (3H)estrone glucosiduronate infusion (39.3 +/- 2.6%) was significantly less than that after (3H)estrone infusion (86.4 +/- 2.3%). The difference was best explained by different rates of formation of unconjugated from conjugated estrogens, suggesting, in turn, that simultaneous uptake and formation of unconjugated estrogens occur in the splanchnic area. The mean splanchnic extraction of extradiol-17alpha-3-glucosiduronate was 33 +/- 3.9%. The mean splanchnic extraction of radioactive estrone glucosiduronate after (3H)estrone glucosiduronate infusion was positive (54.7 +/- 2.3%) and after (3H)estrone infusion was negative (-50.8 +/-8.8%. The mean splanchnic extraction of estradiol-17beta glucosiduronate(s) was also positive (32 +/- 2.4%) after (3H)estrone glucosiduronate infusion and negative (-37.9 +/- 11.0%) after (3H)estrone infusion. These values are taken to indicate that simultaneous uptake and formation (from unconjugated estrogens) of both estrone glucosiduronate and estradiol-17beta glucosiduronate(s) occur in the splanchnic area, and that after (3H)estrone infusion, the rate of formation greatly exceeds t

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Metabolism of 4-14 C-progesterone in the adult female chimpanzee.

The metabolism of 4- 14-C-progesterone was studied in two adult female chimpanzees (Pan troglodytes). After intravenous injection of 4- 14-C-progesterone, urine was collected for 5 days. The urinary conjugates were hydrolyzed with Glusulase and the extracts purified by chromatography on silica gel, paper and alumina and then crystallized to constant specific activity with or without carrier steroid. The major metabolite in both experiments was pregnanediol which accounted for 39.8% and 49.5% of the recovered dose respectively. Pregnanolone (0.6% and 2.1%) and pregnanetriol (0.1% and 1.5%) were also isolated in smaller quantities. These data suggest that the pattern of progesterone metabolism in the chimpanzee is similar to that of man in that pregnanediol is the major metabolite whereas androsterone is not.

Aluminum↗

Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs.

Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made.

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Dynamics of estrone glucosiduronate metabolism in dogs.

Interest in the metabolism of estrogen conjugates has been increased by the recent demonstration that some of these conjugates can be hydrolysed in vivo, and are thus a source of physiologically-active circulating estrogens. In this report the metabolism of the quantitatively important conjugate estrone glucosiduronate has been studied in dogs, following the intravenous infusion of 3H-estrone glucosiduronate. Arterial plasma levels of radioactive estrone glucosiduronate and of the radioactive metabolites estrone, estradiol-17beta-3-glucosiduronate and estradiol-17alpha-3-glucosiduronate were measured. The metabolic clearance rate of estrone glucosiduronate (MCREG) was determined, as well as conversion ratios for estrone glucosiduronate to estrone (CREG.E), estradiol-17beta-3-glucosiduronate (CREG.E2betaG) and estradiol-17alpha-3-glucosiduronate (CREG.E2alphaG). Sequential values for the above mentioned conversion ratios were obtained and the relationship to time was analysed. Transfer constants for estrone glucosiduronate to estrone (rhoEG.E) were measured. The mean MCREG was 329 L/day/m2, SE 35. The values for CREG.E2betaG and CREG.E2alphaG did not become constant until 80 minutes following the start of infusion. The mean values at a steady state were: CREG.E.021, SE .002, CREG.E2betaG .068, SE .005, CREG.E2alphaG .022, SE .002. The mean value for rhoEG.E was .057, SE .006.

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The transfer of glucose to steroids by chimpanzee liver microsomes.

Microsomal preparations from chimpanzee liver can transfer glucose from UDPglucose to the 17alpha-hydroxyl group of 17alpha-estradiol and of 17alpha-estradiol-3-glucuronide. A phenolic glucoside of estrone, but not of either 17alpha- or 17beta-estradiol is also formed. No formation of glucosides of p-nitrophenol, or of diethylstilbestrol was demonstrated. The specificity of glucosyl transfer in the chimpanzee is not identical to that in either the human, the rabbit, or the sheep.

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Identification and measurement of urinary estrone, estradiol-17 beta, estriol, pregnanediol and androsterone during the menstrual cycle of the orangutan.

Urinary estrone, estradiol-17beta, estriol, pregnanediol and androsterone were identified and measured during 3 menstrual cycles in 2 female orangutans. In 2 of the cycles, the animals excreted 1-8 mug/day estrone, 0.5-6 mug/day estradiol-17beta, 1-8 mug/day estriol, 20-206 mug/day pregnanediol and 120-522 mug/day androsterone during the first half of the menstrual cycle. In the second half of the cycle, corresponding values were 3-21 mug/day estrone, 2-10 mug/day estradiol-17beta, 1-9 mug/day estriol, 54-800 mug/day pregnanediol and 90-1158 mug/day androsterone. In 1 cycle, the estrogen values for the second half were considerably higher, possibly due to the animal becoming pregnant just before this study commenced. The values for estrone and estradiol-17beta are similar to those found in the human and chimpanzee menstrual cycle. The values for estriol were lower than in the human but higher than in the chimpanzee. Levels for urinary pregnanediol and androsterone were significantly lower than in the human. Variations during the menstrual cycle for estrone were characterized by a midcycle peak followed by a second peak in the luteal phase. No definite pattern was apparent for estradiol-17beta or estriol. Both urinary pregnanediol and androsterone levels were low during the first half of the cycle, started to rise just after midcycle, and showed a peak during the second half of the menstrual cycle.

Androsterone↗

Hydrolysis of estrogen conjugates by the lungs of the dog in vivo.

Although hydrolysis of certain estrogen conjugates released into the systemic circulation is now known to occur in the human and in the dog, the site or sites of such hydrolysis remained unidentified. In an attempt to identify such sites, radioactive estrone was infused intravenously into a series of male dogs and serial paired samples of blood were obtained from the right ventricle (RV) and a peripheral artery (A). The samples were analysed for total radioactivity, unconjugated radioactive estrogens, radioactive estrone, estradiol-17beta, estrone sulfate, estrone glucosiduronate and estradiol-17beta glucosiduronate(s). The mean percent extraction across the lungs (see article) was calculated for each radioactive moiety analyzed. There was no significant percent extration of total radioactivity or of estrone sulfate. The mean percent extractions for unconjugated estrogens and for estrone and estradiol-17beta were -24.7, -21 and -34.3 respectively (P less than 0.01), indicating net production by the lungs. The mean percent extractions for estrone glucosiduronate and estradiol-17beta glucosiduronate(s) were +19.8 and +10.0 respectively (P less then 0.01), indicating net uptake of these conjugates by the lungs. Statistical analysis showed that the two processes were related. Our findings support the hypothesis that the lungs are one site, possibly the main site, at which hydrolysis of estrogen glucosiduronates occurs in the dog.

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Metabolism of arterial plasma estrogens by the splanchnic organs of the dog in vivo.

In order to study the splanchnic metabolism of blood-borne estrogens, a constant infusion of estrone-6,7-(3)H was made in a series of dogs, and arteriovenous (A-V) differences at equilibrium were determined for estrone-6,7-(3)H and for its products estradiol-17beta, estrone sulfate, estrone glucosiduronate, and estradiol-17beta glucosiduronate across the splanchnic bed (artery-hepatic vein), the small intestine (artery-superior mesenteric vein), and the spleen (artery-splenic vein). Per cent extractions (100 - [V/A] 100) were calculated. The plasma metabolic clearance rate (MCR) for estrone was measured. Principal findings were as follows: mean MCR was 731 liters/day per m(2), SEM 50. By comparison with estimated hepatic plasma flow and using the observed splanchnic extraction of estrone, 45-71% of estrone metabolism was calculated to be extrasplanchnic. The significant mean per cent extractions were as follows (SEM in parentheses): splanchnic bedestrone 85.9 (1.92), estradiol-17beta 88.11 (3.36), estrone sulfate 27.9 (5.22), estrone glucosiduronate -48.5 (9.33), estradiol-17beta glucosiduronate -33.3 (80.3); small intestine-estrone 45.3 (2.60), estradiol-17beta 46.1 (12.9), estrone glucosiduronate - 30.8 (7.9); spleen-estrone 35 (3.8), estrone glucosiduronate 12 (3.7). These results lead to the following conclusions. Both estrone and estradiol-17beta are nearly completely extracted in one passage through the splanchnic bed. There is net uptake of estrone sulfate and net production of estrone glucosiduronate and of estradiol-17beta glucosiduronate by the splanchnic bed. There is net uptake of estrone and of estradiol-17beta by the intestine, associated with substantial net production of estrone glucosiduronate. There is net uptake of estrone by the spleen and a small but significant net uptake of estrone glucosiduronate.

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