METABOLISM OF DEHYDROEPIANDROSTERONE SULPHATE AND OESTRONE SULPHATE FOLLOWING IN SITU PLACENTAL PERFUSION AT MIDPREGNANCY

1971 ◽  
Vol 66 (4) ◽  
pp. 637-647 ◽  
Author(s):  
J. Schwers ◽  
T. Vancrombreucq ◽  
M. Govaerts ◽  
G. Eriksson ◽  
E. Diczfalusy

ABSTRACT Two midgestation placentas were perfused in situ with a combination of [7α-3H] dehydroepiandrosterone sulphate and [4-14C] oestrone sulphate and metabolites were isolated from the placentas, perfusates and maternal urine specimens. Approximately 70 per cent of the perfused radioactive material was recovered from these three sources. The bulk of the administered radioactive material was recovered in an unchanged form from the perfusates; some 2–4 per cent was excreted in the urine and less than 0.5% was found in the placentas. The tritium to carbon-14 ratio of the unconjugated material isolated from the perfusates and placentas was higher, and that of the conjugated material recovered from the same sources was lower than the ratio of the administered material. In addition, more tritium than carbon-14 labelled material was present in the urine. Approximately 2 per cent of the perfused dehydroepiandrosterone sulphate was recovered in the form of phenolic steroids, mostly from the urine. From this source double labelled oestrone, oestriol, 16α-hydroxy-oestrone and 16-epioestriol were isolated. The tritium to carbon-14 ratio of all oestrogens isolated from the urine was higher than that of the perfused material. From the urine specimens 10 to 15 times more double labelled oestriol than oestrone was isolated.

1972 ◽  
Vol 70 (1) ◽  
pp. 132-142 ◽  
Author(s):  
U. Goebelsmann ◽  
J. M. Roberts ◽  
R. B. Jaffe

ABSTRACT Four human placentas were perfused in situ at midpregnancy, two with biosynthetically prepared 3H-oestriol-16-glucosiduronate-14C (OE3-16Gl) and two with 3H-oestriol-3-sulphate-16-glucosiduronate (OE3-3S,16Gl). The radioactive material recovered from the placentas, perfusates and maternal urine was quantitated and identified. Only 0.8 to 3.7% of the labelled material administered was recovered from urine specimens; the bulk of the labelled material perfused was found in the extracts of placentas and perfusates. The double-labelled material isolated from the three sources following perfusion with 3H-OE3-16Gl-14C was identified as OE3-16Gl. The 3H/14C ratios measured in these fractions were virtually identical with those of the tracers perfused. Following perfusion with 3H-OE3-3S,16Gl, three-fourths of the 3H-labelled material recovered from the urine was identified as OE3-3S,16Gl and a small but significant portion of the tritiated material extracted from the placentas and perfusates was shown to be 3H-OE3-16Gl. No significant quantities of unconjugated labelled material could be detected in any of the four placental perfusions. The data presented provide conclusive evidence that both OE3-16Gl and OE3-3S,16Gl are transferred across the placenta in situ without previous hydrolysis. The placenta in vivo is capable of converting some OE3-3S,16Gl to OE3-16Gl. The latter conjugate remains unhydrolysed.


1968 ◽  
Vol 59 (3) ◽  
pp. 426-432 ◽  
Author(s):  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Two human placentas were perfused in situ at midpregnancy with a combination of oestriol-15-3H-3-glucosiduronate (OE3-3Gl) and oestriol-16-14C-16-glucosiduronate (OE3-16Gl) and the radioactive material recovered from the placentas, perfusates and urine specimens was analysed. Only 1 to 2 per cent of the tracers administered was recovered from the urine; the bulk of the administered material was found in the perfusates and placentas. Under the experimental conditions used, no evidence for the metabolism of the two conjugates was found. The OE33Gl isolated from the three sources contained only 3H-label, and the OE3-16Gl only 14C-label. Whereas the evidence indicating the placental transfer of OE3-16Gl in an unchanged form is circumstantial, conclusive evidence is presented that OE3-3Gl is transferred across the placenta without hydrolysis.


1971 ◽  
Vol 66 (4) ◽  
pp. 653-665 ◽  
Author(s):  
G. Benagiano ◽  
M. Ermini ◽  
B. de la Torre ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Three midgestation placentas were perfused at laparotomy during fifteen minutes with tracer amounts of [1,2-3H] testosterone [35S] sulphate sodium salt, and metabolites present in the placentas, perfusates and maternal urine specimens were analyzed. Most of the radioactive material administered was present in the placentas and perfusates; approximately 2% of it was recovered from the urine. More than 99.5% of the radioactive material recovered from the placentas and the perfusates was in a water soluble (conjugated) form. No unconjugated testosterone was found in these sources. Radiochemically homogeneous [1,2-3H] testosterone [35S] sulphate was isolated from the placentas, perfusates and urine specimens collected during the first 24 hours of experiment. The isotopic ratio of the conjugate isolated from these sources was very similar to that of the perfused material. Seventy per cent of the double labelled radioactive material recovered from the Day 1 urine samples was radiochemically homogeneous testosterone sulphate. The relative amounts of testosterone sulphate present in the Day 2 and Day 3 urine specimens showed a gradual decrease. This decrease was associated with an increase in tritium to sulphur-35 ratio. From the pooled extracts of all urine specimens, small amounts of exclusively tritium labelled conjugated 5α-androsterone and 5β-androsterone were also isolated. No 17β-oestradiol 17-sulphate was detected in any of the sources studied. It is concluded that little, if any, testosterone sulphate is hydrolyzed by the midgestation human placenta, and that a considerable part of the testosterone sulphate secreted by the foetus is transferred across the placenta to the mother in an unchanged form. The major part of the transferred testosterone sulphate is excreted in the urine; a smaller part of it undergoes hydrolysis with a subsequent metabolism of the steroid moiety.


1965 ◽  
Vol 49 (2) ◽  
pp. 248-261 ◽  
Author(s):  
S. Mancuso ◽  
Francesca P. Mancuso ◽  
K.-G. Tillinger ◽  
E. Diczfalusy

ABSTRACT Two amenorrhoeic women were given a course of 10 injections of human menopausal gonadotrophin (HMG) in daily doses corresponding to 260 IU of follicle stimulating hormone (FSH) activity and 165 IU of interstitial cell stimulating hormone (ICSH) activity. In both patients an extensive ovarian stimulation was observed as indicated by the greatly increased urinary excretion of oestrone, 17β-oestradiol and oestriol. When HMG-treatment was followed subsequently by the administration of human chorionic gonadotrophin (HCG) for 5 days in a total dose of 18 000 and 30 000 IU, respectively, functional corpus luteum tissue was formed in both patients as evidenced by a huge rise in urinary pregnane-3α,20α-diol excretion and by the secretory transformation of a previously atrophic endometrium. At the approximate height of the follicular phase tracer doses of 3H-labelled dehydroepiandrosterone sulphate (DHAS) and 14C-labelled dehydroepiandrosterone (DHA) were administered to both patients in the form of a continuous intravenous infusion of 10 hours' duration. Infusion of the same dose was repeated under identical experimental conditions at the approximate height of the luteal phase. In both patients, very little radioactive material was associated with oestrone and 17β-oestradiol and none with oestriol isolated from 96-hours' urine specimens obtained at both phases of ovarian stimulation. It is concluded that — in contradistinction to the situation in pregnant women — circulating DHAS is not a significant precursor of urinary oestrogens in non-pregnant women.


1970 ◽  
Vol 65 (1) ◽  
pp. 69-83 ◽  
Author(s):  
H. Vokal ◽  
D. F. Archer ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT The following steroids, [7α-3H]5-androstene-3β,16α,17β-triol and [4-14C] 5-androstene-3β,16β,17β-triol were biosynthesized and their metabolism was studied in two subjects at midgestation, following placental perfusion in situ. Among the metabolites isolated in a radiochemically homogeneous form, exclusively 3H-labelled 16α,17β-dihydroxy-4-androsten-3-one was isolated from the extracts of placentas and perfusates. Exclusively 14C-labelled 16β,17β-dihydroxy-4-androsten-3-one was isolated from the placentas and perfusates and 16-epioestriol (1,3,5(10)-oestratriene-3,16β,17β-triol) from the placentas, perfusates and urine specimens. The following compounds contained both 3H and 14C-label: oestriol (placentas and urine specimens) and 5β-androstane-3α,16α,17β-triol (urine specimens). The 3H/14C-ratio of oestriol isolated from the urine specimens was much lower than that of urinary 5β-androstane-3α,16α,17β-triol, or that of the oestriol isolated from the placentas. The 3H/14C-ratio of the oestriol isolated from the urine 2–4 days following the perfusion was lower than that of the perfused material. It is concluded that a considerable amount of the 16-epioestriol secreted by the placenta is gradually converted to oestriol by the maternal organism. A limited conversion occurs also in the placenta.


1964 ◽  
Vol 45 (2) ◽  
pp. 297-320 ◽  
Author(s):  
R. C. Haynes ◽  
G. Mikhail ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Five normal previable foetuses were perfused with tracer amounts of oestradiol-4-14C and the metabolism of the compound was investigated. This study was completed by 3 experiments in which the oestradiol-4-14C was introduced in situ into the intact foeto-placental unit via the umbilical circulation. More than 80 per cent of the radioactive material present in the various foetal organs in both types of experiments was in a conjugated form. In contrast, in the placentas, less than 10 per cent of the total radioactivity present was in a conjugated form. The bulk of the radioactive material present in the foetal tissues was identified as oestradiol 3-sulphate and oestrone sulphate. In addition, two minor fractions were detected in the perfused foetuses, one of which behaved in countercurrent distribution studies as »glucosiduronates«; the other resembled »sulphates«. The oestrogen moiety of these two fractions was neither oestradiol nor oestrone, but it appeared to be a complex mixture. Although some radioactive material was found which closely resembled oestriol, it was not possible to detect oestriol with certainty. No glucosiduronate-like material was found in the foetal tissues following the injection of oestradiol-4-14C into the intact foeto-placental unit. Also the quantity of the »sulphate-like« material different from oestradioland oestrone sulphates was greatly reduced: A number of unconjugated metabolites were also detected, among which oestrone was identified. A perfusion experiment with an anencephalic foetus indicated that this foetus was capable of forming conjugated metabolites from oestradiol-4-14C. The results obtained do not favour the view that oestriol is a major and instantaneously formed foetal metabolite of oestradiol. On the other hand, they lend additional support to the concept that oestrogens reaching the foetus are extensively sulphurylated by the foetus and that these oestrogen sulphates are hydrolysed by the placenta before transfer of the oestrogen moiety to the maternal circulation.


1967 ◽  
Vol 56 (1) ◽  
pp. 71-84 ◽  
Author(s):  
G. Zucconi ◽  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Oestrone-6,7-3H-glucosiduronate-14C (OE1-3H-Gl-14C) has been prepared biosynthetically and its metabolism studied in two cases of therapeutic abortion following the administration of the tracer at laparotomy into the umbilical vein. The bulk of the radioactive material recovered was in the foetus and placenta; only small amounts were present in the urine of the mother. Minute quantities of the radioactive material recovered from any of these sources were in an unconjugated form. Following reduction with KBH4 of the extract of the foetal liver oestriol-3-glucosiduronate (OE3-3Gl) was isolated from this source with the same isotopic ratio as that of the injected material. Following hydrolysis with β-glucuronidase, 3H-labelled oestrone, 17β-oestradiol and oestriol were isolated in a radiochemically homogeneous form from the foetal liver and from the urine of the mother, and oestrone and 17β-oestradiol from the placenta. From the urine of the mothers OE1-3H-Gl-14C was also isolated. It exhibited the same isotopic ratio as the injected material. Following the intravenous infusion to two women at midpregnancy of a combination of 3H-labelled OE1-Gl and 14C-labelled oestrone sulphate (OE1-S), the tracer administered as OE1-Gl was eliminated in the urine far more rapidly than that infused in the form of OE1-S. It is concluded that at midpregnancy a) the foetus is capable of metabolizing OE1-Gl without any preceding hydrolysis, b) the placenta exhibits no β-glucuronidase activity, c) only a limited amount of OE1-Gl is transferred from the foeto-placental circulation to the mother and exclusively in an unchanged form, and d) OE1-Gl is eliminated from the maternal circulation much more rapidly than OE1-S.


1964 ◽  
Vol 45 (4) ◽  
pp. 535-559 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT In 15 cases of therapeutic abortion by laparotomy the placenta was disconnected from the foetus and perfused in situ with tracer amounts of radioactive dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), androst-4-ene-3,17-dione (A), testosterone (T) and 17β-oestradiol (OE2). Analysis of the placentas, perfusates and urine samples revealed an extensive aromatisation of DHA, A and T; more than 70% of the radioactive material recovered was phenolic, and at least 80 % of this phenolic material was identified as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3), the latter being detected only in the urine. Comparative studies indicated that A and T were aromatised somewhat better than DHA and that all three unconjugated steroids were aromatised to a much greater extent than DHAS. Radioactive OE1 and OE2 were isolated and identified in the placentas and perfusates, but no OE3, epimeric oestriols, or ring D ketols could be detected in these sources, not even when human chorionic gonadotrophin (HCG) was added to the blood prior to perfusion. Lack of placental 16-hydroxylation was also apparent when OE2 was perfused. Regardless of the precursor perfused, there was three times more OE2 than OE1 in the placenta and three times more OE1 than OE2 in the perfusate. This was also the case following perfusion with OE2. The results are interpreted as suggesting the existence in the pregnant human of a placental »barrier« limiting the passage of circulating androgen. The barrier consists of a) limited ability to transfer directly DHAS and b) an enzymic mechanism resulting in the rapid and extensive aromatisation of the important androgens DHA, A and T.


2020 ◽  
Vol 13 ◽  
pp. 262
Author(s):  
K. L. Karfopoulos ◽  
G. N. Papadakos ◽  
D. J. Karangelos ◽  
P. K. Rouni ◽  
N. P. Petropoulos ◽  
...  

It is estimated that until 1978 about 200000 lightning conductor rods with -a emitting sources attached to their end were installed worldwide. The sources were supposed to increase the lighting collection efficiency of these rods through the ionization of the surrounding air. Nevertheless, this improvement has never been established conclusively. Such devices are, in most cases, not accessible by the pub- lic; therefore, the dose to the population is considered insignificant. However, the possibility of radioactive material leakage, due to the source attachment failure, and the subsequent contamination of the surroundings that could lead to possible health risk of the public cannot be excluded. In this work, the case of 241Am contamination due to a lightning rod conductor failure is investigated. This contamination was accidentally detected on the surface soil around a laboratory building in the National Technical University of Athens Campus, during a routine in-situ gamma-ray measurement campaign that took place in 2003. A detailed survey revealed that this 241Am contamination was due to the leakage from two lightning rods on the building roof. Consequently the rods were removed from the building and the contamination pattern on the roof and on the surface soil around the building was examined in detail. From the results obtained so far it may be concluded that there exists well localized contamination on the roof and also around the building. It was established that the pathway through which contamination reached the ground was  the rainwater drainage system of the building. The gamma ray dose rate due to 241Am contamination found on the roof and on the surface soil is low compared to that due to its natural radioactivity and does not seem to pose any health risk to the people working in the building or to the public.


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