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.

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.

STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1965 ◽  
Vol 48 (3) ◽  
pp. 413-422 ◽  
Author(s):  
R. Jaffea ◽  
R. Pionb ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Experimental Techniques ◽  
Antecubital Vein ◽  
Term Administration

ABSTRACT Using a variety of experimental techniques, including perfusion of placentas in situ, injection into the intact foeto-placental unit via the umbilical vein, as well as long-term administration into the amniotic sac or antecubital vein of the mother, very little if any oestrone, 17β-oestradiol- or oestriol-like radioactive material could be detected in the placenta, foetal tissues and urine of the mother following the administration of labelled progesterone. The results are interpreted as supporting the concept that progesterone is not a significant precursor of placental oestrogens.

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 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.

Platelet and Shear Rate Promote Tumor Cell Adhesion to Human Endothelial Extracellular Matrix - Absence of a Role for Platelet Cyclooxygenase

1989 ◽  
Vol 61 (03) ◽  
pp. 485-489 ◽  
Author(s):  
Eva Bastida ◽  
Lourdes Almirall ◽  
Antonio Ordinas
Keyword(s):  
Cell Adhesion ◽  
Shear Rate ◽  
Tumor Cell ◽  
Umbilical Vein ◽  
Blood Platelets ◽  
Flow Conditions ◽  
Tumor Cell Adhesion ◽  
Rate Dependent ◽  
Static Conditions

SummaryBlood platelets are thought to be involved in certain aspects of malignant dissemination. To study the role of platelets in tumor cell adherence to vascular endothelium we performed studies under static and flow conditions, measuring tumor cell adhesion in the absence or presence of platelets. We used highly metastatic human adenocarcinoma cells of the lung, cultured human umbilical vein endothelial cells (ECs) and extracellular matrices (ECM) prepared from confluent EC monolayers. Our results indicated that under static conditions platelets do not significantly increase tumor cell adhesion to either intact ECs or to exposed ECM. Conversely, the studies performed under flow conditions using the flat chamber perfusion system indicated that the presence of 2 × 105 pl/μl in the perfusate significantly increased the number of tumor cells adhered to ECM, and that this effect was shear rate dependent. The maximal values of tumor cell adhesion were obtained, in presence of platelets, at a shear rate of 1,300 sec-1. Furthermore, our results with ASA-treated platelets suggest that the role of platelets in enhancing tumor cell adhesion to ECM is independent of the activation of the platelet cyclooxygenase pathway.

Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

1997 ◽  
Vol 77 (03) ◽  
pp. 577-584 ◽  
Author(s):  
Mehrdad Baghestanian ◽  
Roland Hofbauer ◽  
Hans G Kress ◽  
Johann Wojta ◽  
Astrid Fabry ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mast Cells ◽  
Umbilical Vein ◽  
Vascular Cells ◽  
Migratory Response ◽  
Thrombin Activation ◽  
Umbilical Vein Endothelial Cells ◽  
Primary Tissue ◽  
Local Expression

SummaryRecent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine-(HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 ± 344 cells [100 ± 11.4%] vs. MGF, 100 ng/ml: 8806 ± 1019 [291 ± 34%] vs. HAUEC: 9703 ± 1506 [320.8 ± 49.8%] vs. HUTMEC: 8950 ± 1857 [295.9 ± 61.4%] vs. HSMEC: 9965 ± 2018 [329.4 ± 66.7%] vs. HUVEC: 9487 ± 1402 [313.6 ± 46.4%], p <0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

LACK OF AROMATISATION OF CIRCULATING DEHYDROEPIANDROSTERONE AND DEHYDROEPIANDROSTERONE SULPHATE IN AMENORRHOEIC WOMEN STIMULATED WITH HUMAN GONADOTROPHINS

1965 ◽  
Vol 49 (2) ◽  
pp. 248-261 ◽  
Author(s):  
S. Mancuso ◽  
Francesca P. Mancuso ◽  
K.-G. Tillinger ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Ovarian Stimulation ◽  
Interstitial Cell ◽  
Follicular Phase ◽  
Radioactive Material ◽  
Dehydroepiandrosterone Sulphate ◽  
Experimental Conditions ◽  
Human Menopausal Gonadotrophin ◽  
Urine Specimens ◽  
Stimulating Hormone

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.

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