METABOLISM OF OESTRONE AND OESTRADIOL IN THE HUMAN FOETO-PLACENTAL UNIT AT MIDPREGNANCY

1965 ◽  
Vol 49 (1) ◽  
pp. 65-82 ◽  
Author(s):  
J. Schwers ◽  
G. Eriksson ◽  
E. Diczfalusy
Keyword(s):  
Isotopic Ratio ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Isotopic Ratios ◽  
Therapeutic Abortion ◽  
Main Site ◽  
Foetal Liver ◽  
Different Sources

ABSTRACT In four cases of therapeutic abortion by laparotomy, tracer amounts of oestrone-6,7-3H and 17β-oestradiol-16-14C were injected into the umbilical vein 20 minutes prior to the interruption of gestation, and the radioactive material recovered from the placenta and various foetal tissues was analysed. More than 92 per cent of the radioactive material recovered from the foetus, but less than 15 per cent of that present in the placenta, was in a conjugated form. Among the foetal tissues studied, the highest percentage of unconjugated (free) radioactive material (25 per cent) occurred in the adrenals. Determination of the isotopic ratios revealed that complete interconversion of injected material was approached only by the oestrone and 17β-oestradiol isolated from the conjugated fraction of the liver. Approximately 10 per cent of the radioactive material recovered from the foetal liver and smaller amounts of that found in the placenta and residual foetal tissues were isolated and identified as oestriol. The isotopic ratio of oestriol isolated from different sources approached very closely that of conjugated oestrone and 17β-oestradiol in the foetal liver, but was distinctly different from the isotopic ratio of free and conjugated oestrone and 17β-oestradiol in all other tissues. At least 9 additional metabolites were detected in the conjugated fraction of the foetal liver. One of them was identified as 15α-hydroxy-17β-oestradiol, another one as 16- (or possibly 17-) epioestriol, and two were ring D ketolic oestrogens, most probably 16α-hydroxyoestrone and 16-oxo-17β-oestradiol. The isotopie ratios of all identified compounds were similar to those of oestrone and 17β-oestradiol isolated from the same fraction. It is concluded that in the foeto-placental unit at midpregnancy, the liver is the main site of oestrone and 17β-oestradiol metabolism and that this metabolism takes place predominantly in a conjugated form, most probably in form of 3-sulphates.

METABOLISM OF OESTRONE GLUCOSIDURONATE AT MIDPREGNANCY

1967 ◽  
Vol 56 (1) ◽  
pp. 71-84 ◽  
Author(s):  
G. Zucconi ◽  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Intravenous Infusion ◽  
Isotopic Ratio ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Therapeutic Abortion ◽  
Maternal Circulation ◽  
Glucuronidase Activity ◽  
Oestrone Sulphate ◽  
Foetal Liver ◽  
Unchanged Form

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.

FATE OF OESTRIOL-3-SULPHATE AND OESTRIOL-16-GLUCOSIDURONATE IN THE INTACT FOETO-PLACENTAL UNIT AT MIDPREGNANCY

1966 ◽  
Vol 53 (3) ◽  
pp. 391-400 ◽  
Author(s):  
U. Goebelsmann ◽  
G. Eriksson ◽  
E. Diczfalusy ◽  
M. Levitz ◽  
G. P. Condon
Keyword(s):  
Umbilical Vein ◽  
The Other ◽  
Radioactive Material ◽  
Therapeutic Abortion ◽  
Maternal Urine ◽  
Other Hand

ABSTRACT In two cases of therapeutic abortion by laparotomy, tracer amounts of 3H-labelled oestriol-3-sulphate (OE3-3S) and 14C-labelled oestriol-16-glucosiduronate (OE3-16GI) were injected into the umbilical vein 15 minutes prior to the interruption of gestation and the radioactive material recovered from the maternal urine, placenta, various foetal tissues and urine was analysed. Some four times more 3H- than 14C-labelled material was excreted in the urine of the mothers. Approximately 90% of both isotopes was identified as OE3-16GI. From the placentas more than twice as much 14C- as 3H-labelled meterial was recovered. All the 14C-labelled material was present in the form of glucosiduronate. Approximately 40% of the 3H-labelled material was identified as unconjugated oestriol (OE3), some 2% was present in the form of unidentified unconjugated material, and the rest was OE3-3S.3-3S. All the 3H-labelled material present in the foetal organism was identified as OE3-3S, indicating lack of metabolism of this conjugate by the foetus. On the other hand, the 14C-labelled OE3-16GI was metabolised by the foetus. A small part of it was converted into OE3-3S, which was present only in the liver. In addition, all foetal tissues contained considerable quantities of 14C-labelled oestriol-3-sulphate,16-glucosiduronate (OE3-3S,16GI) accompanied by smaller amounts of a 14C-labelled glucosiduronate of OE3, which was considerably more polar than OE3-16GI. The foetal urine contained only 14C-labelled glucosiduronates of OE3.

METABOLISM OF OESTRONE SULPHATE BY THE PREVIABLE HUMAN FOETUS

1965 ◽  
Vol 50 (4) ◽  
pp. 597-610 ◽  
Author(s):  
J. Schwers ◽  
Myriam Govaerts-Videtsky ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Isotopic Ratio ◽  
Radioactive Material ◽  
List Type ◽  
Human Foetus ◽  
Oestrone Sulphate ◽  
Foetal Liver ◽  
Polar Metabolites ◽  
Free Material ◽  
Uptake And Metabolism ◽  
Conjugated Metabolites

ABSTRACT Two previable foetuses (20th week of gestation) were perfused with a combination of oestrone-6,7-3H and oestrone-16-14C sulphate. Approximately 80 per cent of the perfused radioactive material was recovered from the various foetal tissues and perfusates in both experiments. In contrast to the 3H-labelled material, very little 14C-labelled material was recovered from the various foetal tissues, except from the liver, which showed an approximately equal uptake of the two isotopes. Thirty-six per cent of the 3H- and as much as 68 per cent of the 14C-labelled material administered was recovered from the perfusate. No 14C-labelled material was detected in any of the extracts of the foetal tissues and perfusates as unconjugated (free) material. No oestriol or 15α-hydroxy-17β-oestradiol could be isolated from the extracts of any of the foetal tissues, except from the liver, where these compounds were present mainly, if not exclusively, as conjugated material. Approximately 10 per cent of the 3H- and 14C-labelled conjugated material recovered from the liver was isolated as oestriol and some 5 per cent of it as 15α-hydroxy-17β-oestradiol. The isotopic ratio (3H/14C) of these compounds was lower than that of oestrone and 17β-oestradiol isolated from the same fraction. Very little, if any oestriol or 15α-hydroxy-17β-oestradiol was detected in the extracts of perfusates. On the other hand, large quantities of some ketonic precursors of oestriol, 15α-hydroxy-17β-oestradiol and of additional highly polar metabolites were present. Following reduction, oestriol was isolated and 15α-hydroxy-17β-oestradiol identified in the extracts of perfusates. The isotopie ratio of these two compounds was similar to the isotopie ratio of those found in the liver. It is concluded that the midterm human foetus is not capable of hydrolysing oestrogen sulphates in the foetal organism oestrone sulphate is mostly taken up by the foetal liver, where the extent of its uptake and metabolism is at least as great as that of oestrone 15α- and 16α-hydroxylation of oestrone takes place mainly, if not exclusively, in the foetal liver and predominantly in form of conjugated material the 15α- and 16α-hydroxylated conjugated metabolites formed from oestrone sulphate are released by the foetal liver into the foetoplacental circulation mainly as ketonic intermediates, rather than completely reduced compounds.

STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1964 ◽  
Vol 45 (4) ◽  
pp. 576-599 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Specific Activity ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Placental Barrier ◽  
Therapeutic Abortion ◽  
Antecubital Vein

ABSTRACT In connection with therapeutic abortion, in two patients tracer amounts of dehydroepiandrosterone-4-14C sulphate (DHAS-4-14C) were injected into the umbilical vein and tracer amounts of dehydroepiandrosterone-7α-3H sulphate (DHAS-7α-3H) into an antecubital vein. The over-all aromatisation of the two labelled compounds in the presence of viable foetuses was studied by analysing the radioactive metabolites excreted in the urine during a period of 6 days. More than 25 per cent of the 3H-labelled metabolites and more than 75 per cent of the 14C-labelled metabolites recovered from the urine were phenolic in character. More than half of this phenolic radioactive material behaved as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3) when analysed by a modified Brown (1955) method. The OE3 to OE1 + OE2 ratio expressed as 14C incorporated into these three fractions was significantly higher in both patients than the corresponding ratio of 3H. Also the 3H to 14C ratio of urinary OE1 significantly exceeded that of OE3. The specific activity (S. A.) of OE3-7α-3H was by far lower than that of OE1-7α-3H, whereas the S. A. of OE3-4-14C differed much less from that of OE1-4-14C. A concept is presented describing the placental barrier to circulating androgen and the role of the placenta in the formation of OE1, OE2 and OE3.

METABOLISM OF 17β-OESTRADIOL-17α-3H BY THE PREVIABLE HUMAN FOETUS AT MIDTERM

1970 ◽  
Vol 63 (1) ◽  
pp. 39-49 ◽  
Author(s):  
G. Benagiano ◽  
S. Mancuso ◽  
B. de la Torre ◽  
E. Diczfalusy
Keyword(s):  
The Other ◽  
Significant Part ◽  
Isotopic Ratios ◽  
Human Foetus ◽  
Homogeneous Form ◽  
Other Hand ◽  
Foetal Liver ◽  
Different Sources ◽  
Direct Hydroxylation

ABSTRACT One female and one male foetus were perfused at midpregnancy with 17β-oestradiol-16-14C,17α-3H and metabolites were isolated in a radiochemically homogeneous form from the perfusates and various foetal tissues. The 3H/14C ratio of the perfused material was 60.2. Unconjugated and conjugated 17β-oestradiol and oestrone were isolated from all tissues studied. The 3H/14C ratio of the oestradiol isolated from all tissues, except the liver, agreed with the perfused one. The oestrone isolated from different sources did not contain any 3H-label. Unconjugated oestriol and conjugated oestriol, 16-epi-oestriol, 16α-hydroxy-oestrone, 16-oxo-oestradiol and 15α-hydroxy-oestradiol were isolated from the extracts of the livers. No 3H-label was present in 16α-hydroxy-oestrone, and only traces, if any, in 16-oxo-oestradiol. On the other hand, the isotopic ratios of 16-epi-oestriol, oestriol and 15α-hydroxy-oestradiol were between 1.5 and 5.0. It is concluded that a small but significant part of the oestriol, 16-epi-oestriol and 15α-hydroxy-oestradiol synthesized by the foetal liver is formed via a direct hydroxylation of oestradiol.

STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1964 ◽  
Vol 45 (4) ◽  
pp. 535-559 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Comparative Studies ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Radioactive Material ◽  
Placental Barrier ◽  
Therapeutic Abortion ◽  
Limited Ability ◽  
Better Than

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.

scholarly journals Determination of platelet antigens and glycoproteins in the human fetus

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 488-492 ◽  
Author(s):  
Y Gruel ◽  
B Boizard ◽  
F Daffos ◽  
F Forestier ◽  
J Caen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Fetus ◽  
Antenatal Diagnosis ◽  
Polyclonal Antibodies ◽  
Umbilical Vein ◽  
Membrane Surface ◽  
Platelet Suspension ◽  
Direct Puncture ◽  
Normal Human

Abstract The autosomal recessive transmission of Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS), together with requests of families who already had children with these diseases, prompted us to investigate the feasibility of their antenatal diagnosis. The preliminary step leading to the early detection of GT or BSS was to characterize, in the normal human fetus, the platelet antigens and glycoproteins (GPs) and to define their normal amounts on the membrane surface. Blood samples from 32 fetuses between 18 to 26 weeks of gestation were collected by direct puncture of the umbilical vein using an ultrasound-guided needle. Polyclonal antibodies from human origin directed against PLA1, Leka antigens, and the GPIIb IIIa complex (IgGL), or murine monoclonal antibodies specific for GPIb (AN51, 6D1), GPIIIa (AP-3), or GPIIb IIIa (AP-2) were studied using platelet suspension immunofluorescence tests. The binding of each antibody was quantified using a cytofluorograph (Ortho 50H). PLA1 and Leka antigens were expressed in normal amounts on fetal platelets as early as 16 weeks of intrauterine life. The GPIIb IIIa complex quantified by polyclonal or monoclonal antibodies was in the same range in fetuses (IgGL = 427 +/- 23 AUF, AP-2 = 459.5 +/- 8.5; AP-3 = 536 +/- 14) and in adults (IgGL = 420 +/- 30; AP-2 = 498 +/- 11; AP-3 = 515 +/- 13). The platelet binding of antibodies that recognized GPIb was higher in fetuses (AN51 = 491.5 +/- 14; 6D1 = 479 +/- 15) than in adults (AN51 = 426.5 +/- 9; 6D1 = 449 +/- 8.7). These results suggest that immunological techniques can be applied as early as 18 weeks of gestation for the antenatal diagnosis of GT and BSS.

Determination of lead isotopic ratios in Greenland and Antarctic snow and ice at picogram per gram concentrations

1995 ◽  
Vol 311 (2) ◽  
pp. 141-151 ◽  
Author(s):  
W. Chisholm ◽  
K.J.R. Rosman ◽  
C.F. Boutron ◽  
J.P. Candelone ◽  
S. Hong
Keyword(s):  
Isotopic Ratios ◽  
Antarctic Snow ◽  
Lead Isotopic Ratios ◽  
Snow And Ice
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